Cell. 2020 Dec 10;183(6):1714-1731.e10. doi: 10.1016/j.cell.2020.10.038.
Abstract: Targeted protein degradation (TPD) refers to the use of small molecules to induce ubiquitin-dependent degradation of proteins. TPD is of interest in drug development, as it can address previously inaccessible targets. However, degrader discovery and optimization remains an inefficient process due to a lack of understanding of the relative importance of the key molecular events required to induce target degradation. Here, we use chemo-proteomics to annotate the degradable kinome. Our expansive dataset provides chemical leads for ∼200 kinases and demonstrates that the current practice of starting from the highest potency binder is an ineffective method for discovering active compounds. We develop multitargeted degraders to answer fundamental questions about the ubiquitin proteasome system, uncovering that kinase degradation is p97 dependent. This work will not only fuel kinase degrader discovery, but also provides a blueprint for evaluating targeted degradation across entire gene families to accelerate understanding of TPD beyond the kinome.
View In: PubMed
Nat Chem Biol. 2020 Jun 1. doi: 10.1038/s41589-020-0550-9.
Abstract: Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is commonly overexpressed in human cancers, including pancreatic ductal adenocarcinoma (PDAC). While Pin1 is dispensable for viability in mice, it is required for activated Ras to induce tumorigenesis, suggesting a role for Pin1 inhibitors in Ras-driven tumors, such as PDAC. We report the development of rationally designed peptide inhibitors that covalently target Cys113, a highly conserved cysteine located in the Pin1 active site. The inhibitors were iteratively optimized for potency, selectivity and cell permeability to give BJP-06-005-3, a versatile tool compound with which to probe Pin1 biology and interrogate its role in cancer. In parallel to inhibitor development, we employed genetic and chemical-genetic strategies to assess the consequences of Pin1 loss in human PDAC cell lines. We demonstrate that Pin1 cooperates with mutant KRAS to promote transformation in PDAC, and that Pin1 inhibition impairs cell viability over time in PDAC cell lines.
View In: PubMed
Nature. 2010;463(7280):501-6.
Abstract: In an effort to find new pharmacological modalities to overcome resistance to ATP-binding-site inhibitors of Bcr-Abl, we recently reported the discovery of GNF-2, a selective allosteric Bcr-Abl inhibitor. Here, using solution NMR, X-ray crystallography, mutagenesis and hydrogen exchange mass spectrometry, we show that GNF-2 binds to the myristate-binding site of Abl, leading to changes in the structural dynamics of the ATP-binding site. GNF-5, an analogue of GNF-2 with improved pharmacokinetic properties, when used in combination with the ATP-competitive inhibitors imatinib or nilotinib, suppressed the emergence of resistance mutations in vitro, displayed additive inhibitory activity in biochemical and cellular assays against T315I mutant human Bcr-Abl and displayed in vivo efficacy against this recalcitrant mutant in a murine bone-marrow transplantation model. These results show that therapeutically relevant inhibition of Bcr-Abl activity can be achieved with inhibitors that bind to the myristate-binding site and that combining allosteric and ATP-competitive inhibitors can overcome resistance to either agent alone.
View In: PubMed
Nature. 2009;462(7276):1070-4
Abstract: The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC) is limited by the development of drug-resistance mutations, including the gatekeeper T790M mutation. Strategies targeting EGFR T790M with irreversible inhibitors have had limited success and are associated with toxicity due to concurrent inhibition of wild-type EGFR. All current EGFR inhibitors possess a structurally related quinazoline-based core scaffold and were identified as ATP-competitive inhibitors of wild-type EGFR. Here we identify a covalent pyrimidine EGFR inhibitor by screening an irreversible kinase inhibitor library specifically against EGFR T790M. These agents are 30- to 100-fold more potent against EGFR T790M, and up to 100-fold less potent against wild-type EGFR, than quinazoline-based EGFR inhibitors in vitro. They are also effective in murine models of lung cancer driven by EGFR T790M. Co-crystallization studies reveal a structural basis for the increased potency and mutant selectivity of these agents. These mutant-selective irreversible EGFR kinase inhibitors may be clinically more effective and better tolerated than quinazoline-based inhibitors. Our findings demonstrate that functional pharmacological screens against clinically important mutant kinases represent a powerful strategy to identify new classes of mutant-selective kinase inhibitors.
View In: PubMed
J Biol Chem. 2009;284(12)8023-32.
Abstract: The mammalian target of rapamycin (mTOR) kinase is the catalytic subunit of two functionally distinct complexes, mTORC1 and mTORC2, that coordinately promote cell growth, proliferation, and survival. Rapamycin is a potent allosteric mTORC1 inhibitor with clinical applications as an immunosuppressant and anti-cancer agent. Here we find that Torin1, a highly potent and selective ATP-competitive mTOR inhibitor that directly inhibits both complexes, impairs cell growth and proliferation to a far greater degree than rapamycin. Surprisingly, these effects are independent of mTORC2 inhibition and are instead because of suppression of rapamycin-resistant functions of mTORC1 that are necessary for cap-dependent translation and suppression of autophagy. These effects are at least partly mediated by mTORC1-dependent and rapamycin-resistant phosphorylation of 4E-BP1. Our findings challenge the assumption that rapamycin completely inhibits mTORC1 and indicate that direct inhibitors of mTORC1 kinase activity may be more successful than rapamycin at inhibiting tumors that depend on mTORC1.
View in: PubMed
Powell CE, Du G, Bushman JW, He Z, Zhang T, Fischer ES, Gray NS. Selective degradation-inducing probes for studying cereblon (CRBN) biology. RSC Med Chem. 2021 Jul 6;12(8):1381-1390.
View in: PubMed
Teng M, Jiang J, Ficarro SB, Seo HS, Bae JH, Donovan KA, Fischer ES, Zhang T, Dhe-Paganon S, Marto JA, Gray NS. Exploring Ligand-Directed N-Acyl-N-alkylsulfonamide-Based Acylation Chemistry for Potential Targeted Degrader Development. ACS Med Chem Lett. 2021 Jul 21;12(8):1302-1307.
View in: PubMed
Koikawa K, Kibe S, Suizu F, Sekino N, Kim N, Manz TD, Pinch BJ, Akshinthala D, Verma A, Gaglia G, Nezu Y, Ke S, Qiu C, Ohuchida K, Oda Y, Lee TH, Wegiel B, Clohessy JG, London N, Santagata S, Wulf GM, Hidalgo M, Muthuswamy SK, Nakamura M, Gray NS, Zhou XZ, Lu KP. Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy. Cell. 2021 Aug 6.
View in: PubMed
Seong BKA, Dharia NV, Lin S, Donovan KA, Chong S, Robichaud A, Conway A, Hamze A, Ross L, Alexe G, Adane B, Nabet B, Ferguson FM, Stolte B, Wang EJ, Sun J, Darzacq X, Piccioni F, Gray NS, Fischer ES, Stegmaier K. TRIM8 modulates the EWS/FLI oncoprotein to promote survival in Ewing sarcoma. Cancer Cell. 2021 Jul 22.
View in: PubMed
Tang CC, Castro Andrade CD, O’Meara MJ, Yoon SH, Sato T, Brooks DJ, Bouxsein ML, Martins JDS, Wang J, Gray NS, Misof B, Roschger P, Boulin S, Klaushofer K, Velduis-Vlug A, Vegting Y, Rosen CJ, O’Connell D, Sundberg TB, Xavier RJ, Ung P, Schlessinger A, Kronenberg HM, Berdeaux R, Foretz M, Wein MN. Dual targeting of salt inducible kinases and CSF1R uncouples bone formation and bone resorption. Elife. 2021 Jun 23.
View in: PubMed
Deng J, Thennavan A, Dolgalev I, Chen T, Li J, Marzio A, Poirier JT, Peng D, Bulatovic M, Mukhopadhyay S, Silver H, Papadopoulos E, Pyon V, Thakurdin C, Han H, Li F, Li S, Ding H, Hu H, Pan Y, Weerasekara V, Jiang B, Wang ES, Ahearn I, Philips M, Papagiannakopoulos T, Tsirigos A, Rothenberg E, Gainor J, Freeman GJ, Rudin CM, Gray NS, Hammerman PS, Pagano M, Heymach JV, Perou CM, Bardeesy N, Wong KK. ULK1 inhibition overcomes compromised antigen presentation and restores antitumor immunity in LKB1 mutant lung cancer. Nat Cancer. 2021 May;2(5):503-514.
View in: PubMed
Yang G, Wang J, Tan L, Munshi M, Liu X, Kofides A, Chen JG, Tsakmaklis N, Demos M, Guerrera ML, Xu L, Hunter ZR, Che J, Patterson CJ, Meid KE, Castillo J, Munshi NC, Anderson KC, Cameron M, Buhrlage S, Gray NSS, Treon SPP. The HCK/BTK inhibitor KIN-8194 is active in MYD88 driven lymphomas and overcomes mutated BTKCys481 ibrutinib resistance. Blood. 2021 Jun 16.
View in: PubMed
Arnett A, Moo KG, Flynn KJ, Sundberg TB, Johannessen L, Shamji AF, Gray NS, Decker T, Zheng Y, Gersuk VH, Rahman ZS, Levy DE, Marié IJ, Linsley PS, Xavier RJ, Khor B. The CDK8 inhibitor DCA promotes a tolerogenic chemical immunophenotype in CD4+ T cells via a novel CDK8-GATA3-FOXP3 pathway. Mol Cell Biol. 2021 Jun 14.
View in: PubMed
Wang ES, Verano AL, Nowak RP, Yuan JC, Donovan KA, Eleuteri NA, Yue H, Ngo KH, Lizotte PH, Gokhale PC, Gray NS, Fischer ES. Acute pharmacological degradation of Helios destabilizes regulatory T cells. Nat Chem Biol. 2021 Jun;17(6):711-717.
View in: PubMed
Vervoort SJ, Welsh SA, Devlin JR, Barbieri E, Knight DA, Offley S, Bjelosevic S, Costacurta M, Todorovski I, Kearney CJ, Sandow JJ, Fan Z, Blyth B, McLeod V, Vissers JHA, Pavic K, Martin BP, Gregory G, Demosthenous E, Zethoven M, Kong IY, Hawkins ED, Hogg SJ, Kelly MJ, Newbold A, Simpson KJ, Kauko O, Harvey KF, Ohlmeyer M, Westermarck J, Gray N, Gardini A, Johnstone RW. The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer. Cell. 2021 May 12.
View in: PubMed
Carli ALE, Afshar-Sterle S, Rai A, Fang H, O’Keefe R, Tse J, Ferguson FM, Gray NS, Ernst M, Greening DW, Buchert M. Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells. Proteomics. 2021 May 15.
View in: PubMed
Remenyi J, Naik RJ, Wang J, Razsolkov M, Verano A, Cai Q, Tan L, Toth R, Raggett S, Baillie C, Traynor R, Hastie CJ, Gray NS, Arthur JSC. Generation of a chemical genetic model for JAK3. Sci Rep. 2021 May 12;11(1):10093.
View in: PubMed
Dubiella C, Pinch BJ, Koikawa K, Zaidman D, Poon E, Manz TD, Nabet B, He S, Resnick E, Rogel A, Langer EM, Daniel CJ, Seo HS, Chen Y, Adelmant G, Sharifzadeh S, Ficarro SB, Jamin Y, Martins da Costa B, Zimmerman MW, Lian X, Kibe S, Kozono S, Doctor ZM, Browne CM, Yang A, Stoler-Barak L, Shah RB, Vangos NE, Geffken EA, Oren R, Koide E, Sidi S, Shulman Z, Wang C, Marto JA, Dhe-Paganon S, Look T, Zhou XZ, Lu KP, Sears RC, Chesler L, Gray NS, London N. Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo. Nat Chem Biol. 2021 May 10.
View in: PubMed
Jiang B, Jiang J, Kaltheuner IH, Iniguez AB, Anand K, Ferguson FM, Ficarro SB, Seong BKA, Greifenberg AK, Dust S, Kwiatkowski NP, Marto JA, Stegmaier K, Zhang T, Geyer M, Gray NS. Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma.Eur J Med Chem. 2021 Apr 20;221:113481.
View in: PubMed
Heckler M, Ali LR, Clancy-Thompson E, Qiang L, Ventre KS, Lenehan P, Roehle K, Luoma A, Boelaars K, Peters V, McCreary J, Boschert T, Wang ES, Suo S, Marangoni F, Mempel TR, Long HW, Wucherpfennig KW, Dougan M, Gray NS, Yuan GC, Goel S, Tolaney SM, Dougan SK. Inhibition of CDK4/6 promotes CD8 T-cell memory formation. Cancer Discov. 2021 May 3.
View in: PubMed
Du G, Jiang J, Wu Q, Henning NJ, Donovan KA, Yue H, Che J, Lu W, Fischer ES, Bardeesy N, Zhang T, Gray NS. Discovery of a Potent Degrader for Fibroblast Growth Factor Receptor 1/2. Angew Chem Int Ed Engl. 2021 Apr 29.
View in: PubMed
Jiang B, Gao Y, Che J, Lu W, Kaltheuner IH, Dries R, Kalocsay M, Berberich MJ, Jiang J, You I, Kwiatkowski N, Riching KM, Daniels DL, Sorger PK, Geyer M, Zhang T, Gray NS. Discovery and resistance mechanism of a selective CDK12 degrader. Nat Chem Biol. 2021 Mar 22.
View in: PubMed
Koduri V, Duplaquet L, Lampson BL, Wang AC, Sabet AH, Ishoey M, Paulk J, Teng M, Harris IS, Endress JE, Liu X, Dasilva E, Paulo JA, Briggs KJ, Doench JG, Ott CJ, Zhang T, Donovan KA, Fischer ES, Gygi SP, Gray NS, Bradner J, Medin JA, Buhrlage SJ, Oser MG, Kaelin WG Jr. Targeting oncoproteins with a positive selection assay for protein degraders. Sci Adv. 2021 Feb 5.
View in: PubMed
Sheppard HE, Dall’Agnese A, Park WD, Shamim MH, Dubrulle J, Johnson HL, Stossi F, Cogswell P, Sommer J, Levy J, Sharifnia T, Wawer MJ, Nabet B, Gray NS, Clemons PA, Schreiber SL, Workman P, Young RA, Lin CY. Targeted brachyury degradation disrupts a highly specific autoregulatory program controlling chordoma cell identity. Cell Rep Med. 2021 Jan 19;2(1):100188.
View in: PubMed
Groendyke BJ, Nabet B, Mohardt ML, Zhang H, Peng K, Koide E, Coffey CR, Che J, Scott DA, Bass AJ, Gray NS. Discovery of a Pyrimidothiazolodiazepinone as a Potent and Selective Focal Adhesion Kinase (FAK) Inhibitor. ACS Med Chem Lett. 2020 Dec 14;12(1):30-38.
View in: PubMed
Wells CI, Al-Ali H, Andrews DM, Asquith CRM, Axtman AD, Dikic I, Ebner D, Ettmayer P, Fischer C, Frederiksen M, Futrell RE, Gray NS, Hatch SB, Knapp S, Lücking U, Michaelides M, Mills CE, Müller S, Owen D, Picado A, Saikatendu KS, Schröder M, Stolz A, Tellechea M, Turunen BJ, Vilar S, Wang J, Zuercher WJ, Willson TM, Drewry DH. The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification. Int J Mol Sci. 2021 Jan 8;22(2):E566.
View in: PubMed
Dhimolea E, de Matos Simoes R, Kansara D, Al’Khafaji A, Bouyssou J, Weng X, Sharma S, Raja J, Awate P, Shirasaki R, Tang H, Glassner BJ, Liu Z, Gao D, Bryan J, Bender S, Roth J, Scheffer M, Jeselsohn R, Gray NS, Georgakoudi I, Vazquez F, Tsherniak A, Chen Y, Welm A, Duy C, Melnick A, Bartholdy B, Brown M, Culhane AC, Mitsiades CS. An Embryonic Diapause-like Adaptation with Suppressed Myc Activity Enables Tumor Treatment Persistence. Cancer Cell. 2021 Jan 5.
View in: PubMed
Levine ZG, Potter SC, Joiner CM, Fei GQ, Nabet B, Sonnett M, Zachara NE, Gray NS, Paulo JA, Walker S. Mammalian cell proliferation requires noncatalytic functions of O-GlcNAc transferase. Proc Natl Acad Sci U S A. 2021 Jan 26.
View in: PubMed
Shirasaki R, Matthews GM, Gandolfi S, de Matos Simoes R, Buckley DL, Raja Vora J, Sievers QL, Brüggenthies JB, Dashevsky O, Poarch H, Tang H, Bariteau MA, Sheffer M, Hu Y, Downey-Kopyscinski SL, Hengeveld PJ, Glassner BJ, Dhimolea E, Ott CJ, Zhang T, Kwiatkowski NP, Laubach JP, Schlossman RL, Richardson PG, Culhane AC, Groen RWJ, Fischer ES, Vazquez F, Tsherniak A, Hahn WC, Levy J, Auclair D, Licht JD, Keats JJ, Boise LH, Ebert BL, Bradner JE, Gray NS, Mitsiades CS. Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins.Cell Rep. 2021 Jan 5;34(1):108532.
View in: PubMed
Donovan KA, Ferguson FM, Bushman JW, Eleuteri NA, Bhunia D, Ryu S, Tan L, Shi K, Yue H, Liu X, Dobrovolsky D, Jiang B, Wang J, Hao M, You I, Teng M, Liang Y, Hatcher J, Li Z, Manz TD, Groendyke B, Hu W, Nam Y, Sengupta S, Cho H, Shin I, Agius MP, Ghobrial IM, Ma MW, Che J, Buhrlage SJ, Sim T, Gray NS, Fischer ES. Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development. Cell. 2020 Dec 10;183(6):1714-1731.
View in: PubMed
Hatcher JM, Yang G, Wang L, Ficarro SB, Buhrlage S, Wu H, Marto JA, Treon SP, Gray NS. Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma. ACS Med Chem Lett. 2020 Oct 9;11(11):2238-2243.
View in: PubMed
Poon E, Liang T, Jamin Y, Walz S, Kwok C, Hakkert A, Barker K, Urban Z, Thway K, Zeid R, Hallsworth A, Box G, Ebus ME, Licciardello MP, Sbirkov Y, Lazaro G, Calton E, Costa BM, Valenti M, De Haven Brandon A, Webber H, Tardif N, Almeida GS, Christova R, Boysen G, Richards MW, Barone G, Ford A, Bayliss R, Clarke PA, De Bono J, Gray NS, Blagg J, Robinson SP, Eccles SA, Zheleva D, Bradner JE, Molenaar J, Vivanco I, Eilers M, Workman P, Lin CY, Chesler L. Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma. J Clin Invest. 2020 Oct 05:134132.
View in: PubMed
Powell CE, Du G, Che J, He Z, Donovan KA, Yue H, Wang ES, Nowak RP, Zhang T, Fischer ES, Gray NS. Selective Degradation of GSPT1 by Cereblon Modulators Identified via a Focused Combinatorial Library. ACS Chem Biol. 2020 Sep 28.
View in: PubMed
Nabet B, Ferguson FM, Seong BKA, Kuljanin M, Leggett AL, Mohardt ML, Robichaud A, Conway AS, Buckley DL, Mancias JD, Bradner JE, Stegmaier K, Gray NS. Rapid and direct control of target protein levels with VHL-recruiting dTAG molecules. Nat Commun. 2020 09 18; 11(1):4687.
View in: PubMed
Fan Z, Devlin JR, Hogg SJ, Doyle MA, Harrison PF, Todorovski I, Cluse LA, Knight DA, Sandow JJ, Gregory G, Fox A, Beilharz TH, Kwiatkowski N, Scott NE, Vidakovic AT, Kelly GP, Svejstrup JQ, Geyer M, Gray NS, Vervoort SJ, Johnstone RW. CDK13 cooperates with CDK12 to control global RNA polymerase II processivity. Sci Adv. 2020 Apr 29.
View in: PubMed
Jiang J, Jiang B, He Z, Ficarro SB, Che J, Marto JA, Gao Y, Zhang T, Gray NS. Discovery of Covalent MKK4/7 Dual Inhibitor. Cell Chem Biol. 2020 Sep 07.
View in: PubMed
Weisberg E, Meng C, Case A, Sattler M, Tiv HL, Gokhale PC, Buhrlage S, Wang J, Gray N, Stone R, Liu S, Bhagwat SV, Tiu RV, Adamia S, Griffin JD. Correction: Evaluation of ERK as a therapeutic target in acute myelogenous leukemia. Leukemia. 2020 Sep; 34(9):2543.
View in: PubMed
Ferguson FM, Liu Y, Harshbarger W, Huang L, Wang J, Deng X, Capuzzi SJ, Muratov EN, Tropsha A, Muthuswamy S, Westover KD, Gray NS. Correction to “Synthesis and Structure-Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one Scaffold”. J Med Chem. 2020 Sep 10; 63(17):10088.
View in: PubMed
Weisberg E, Parent A, Yang PL, Sattler M, Liu Q, Liu Q, Wang J, Meng C, Buhrlage SJ, Gray N, Griffin JD. Repurposing of Kinase Inhibitors for Treatment of COVID-19. Pharm Res. 2020 Aug 10; 37(9):167.
View in: PubMed
Schröder M, Tan L, Wang J, Liang Y, Gray NS, Knapp S, Chaikuad A. Catalytic Domain Plasticity of MKK7 Reveals Structural Mechanisms of Allosteric Activation and Diverse Targeting Opportunities. Cell Chem Biol. 2020 Aug 04.
View in: PubMed
Liu Y, Ferguson FM, Li L, Kuljanin M, Mills CE, Subramanian K, Harshbarger W, Gondi S, Wang J, Sorger PK, Mancias JD, Gray NS, Westover KD. Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing. Cell Chem Biol. 2020 Aug 04.
View in: PubMed
Li Z, Powell CE, Groendyke BJ, Gero TW, Feru F, Feutrill J, Chen B, Li B, Szabo H, Gray NS, Scott DA. Discovery of a series of benzopyrimidodiazepinone TNK2 inhibitors via scaffold morphing. Bioorg Med Chem Lett. 2020 Oct 01; 30(19):127456.
View in: PubMed
Ferguson FM, Liu Y, Harshbarger W, Huang L, Wang J, Deng X, Capuzzi SJ, Muratov EN, Tropsha A, Muthuswamy S, Westover KD, Gray NS. Synthesis and Structure-Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one Scaffold. J Med Chem. 2020 Jul 23; 63(14):7817-7826.
View in: PubMed
Weisberg E, Sattler M, Yang PL, Parent A, Gray N, Griffin JD. Current therapies under investigation for COVID-19: potential COVID-19 treatments. Can J Physiol Pharmacol. 2020 Aug; 98(8):483-489.
View in: PubMed
Liu Y, Hao M, Leggett AL, Gao Y, Ficarro SB, Che J, He Z, Olson CM, Marto JA, Kwiatkowski NP, Zhang T, Gray NS. Discovery of MFH290: A Potent and Highly Selective Covalent Inhibitor for Cyclin-Dependent Kinase 12/13. J Med Chem. 2020 Jul 09; 63(13):6708-6726.
View in: PubMed
Klein IA, Boija A, Afeyan LK, Hawken SW, Fan M, Dall’Agnese A, Oksuz O, Henninger JE, Shrinivas K, Sabari BR, Sagi I, Clark VE, Platt JM, Kar M, McCall PM, Zamudio AV, Manteiga JC, Coffey EL, Li CH, Hannett NM, Guo YE, Decker TM, Lee TI, Zhang T, Weng JK, Taatjes DJ, Chakraborty A, Sharp PA, Chang YT, Hyman AA, Gray NS, Young RA. Partitioning of cancer therapeutics in nuclear condensates. Science. 2020 06 19; 368(6497):1386-1392.
View in: PubMed
Giurisato E, Lonardi S, Telfer B, Lussoso S, Risa-Ebrí B, Zhang J, Russo I, Wang J, Santucci A, Finegan KG, Gray NS, Vermi W, Tournier C. Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis. Cancer Res. 2020 Aug 15; 80(16):3319-3330.
View in: PubMed
Fassl A, Brain C, Abu-Remaileh M, Stukan I, Butter D, Stepien P, Feit AS, Bergholz J, Michowski W, Otto T, Sheng Q, Loo A, Michael W, Tiedt R, DeAngelis C, Schiff R, Jiang B, Jovanovic B, Nowak K, Ericsson M, Cameron M, Gray N, Dillon D, Zhao JJ, Sabatini DM, Jeselsohn R, Brown M, Polyak K, Sicinski P. Increased lysosomal biomass is responsible for the resistance of triple-negative breast cancers to CDK4/6 inhibition. Sci Adv. 2020 Jun; 6(25):eabb2210.
View in: PubMed
Jang J, To C, De Clercq DJH, Park E, Ponthier CM, Shin BH, Mushajiang M, Nowak RP, Fischer ES, Eck MJ, Jänne PA, Gray NS. Mutant-Selective Allosteric EGFR Degraders are Effective Against a Broad Range of Drug-Resistant Mutations. Angew Chem Int Ed Engl. 2020 Jun 08.
View in: PubMed
Teng M, Jiang J, He Z, Kwiatkowski NP, Donovan KA, Mills CE, Victor C, Hatcher JM, Fischer ES, Sorger PK, Zhang T, Gray NS. Development of CDK2 and CDK5 Dual Degrader TMX-2172. Angew Chem Int Ed Engl. 2020 Aug 10; 59(33):13865-13870.
View in: PubMed
Pinch BJ, Doctor ZM, Nabet B, Browne CM, Seo HS, Mohardt ML, Kozono S, Lian X, Manz TD, Chun Y, Kibe S, Zaidman D, Daitchman D, Yeoh ZC, Vangos NE, Geffken EA, Tan L, Ficarro SB, London N, Marto JA, Buratowski S, Dhe-Paganon S, Zhou XZ, Lu KP, Gray NS. Identification of a potent and selective covalent Pin1 inhibitor. Nat Chem Biol. 2020 Sep; 16(9):979-987.
View in: PubMed
Jaeger MG, Schwalb B, Mackowiak SD, Velychko T, Hanzl A, Imrichova H, Brand M, Agerer B, Chorn S, Nabet B, Ferguson FM, Müller AC, Bergthaler A, Gray NS, Bradner JE, Bock C, Hnisz D, Cramer P, Winter GE. Selective Mediator dependence of cell-type-specifying transcription. Nat Genet. 2020 07; 52(7):719-727.
View in: PubMed
Hsu A, Duan Q, McMahon S, Huang Y, Wood SA, Gray NS, Wang B, Bruneau BG, Haldar SM. Salt-inducible kinase 1 maintains HDAC7 stability to promote pathologic cardiac remodeling. J Clin Invest. 2020 Jun 01; 130(6):2966-2977.
View in: PubMed
Gurbani D, Du G, Henning NJ, Rao S, Bera AK, Zhang T, Gray NS, Westover KD. Structure and Characterization of a Covalent Inhibitor of Src Kinase. Front Mol Biosci. 2020; 7:81.
View in: PubMed
Fan Z, Devlin JR, Hogg SJ, Doyle MA, Harrison PF, Todorovski I, Cluse LA, Knight DA, Sandow JJ, Gregory G, Fox A, Beilharz TH, Kwiatkowski N, Scott NE, Vidakovic AT, Kelly GP, Svejstrup JQ, Geyer M, Gray NS, Vervoort SJ, Johnstone RW. CDK13 cooperates with CDK12 to control global RNA polymerase II processivity. Sci Adv. 2020 May; 6(18).
View in: PubMed
Fan Z, Devlin JR, Hogg SJ, Doyle MA, Harrison PF, Todorovski I, Cluse LA, Knight DA, Sandow JJ, Gregory G, Fox A, Beilharz TH, Kwiatkowski N, Scott NE, Vidakovic AT, Kelly GP, Svejstrup JQ, Geyer M, Gray NS, Vervoort SJ, Johnstone RW. CDK13 cooperates with CDK12 to control global RNA polymerase II processivity. Sci Adv. 2020 May; 6(18):eaaz5041.
View in: PubMed
Gasic I, Groendyke BJ, Nowak RP, Yuan JC, Kalabathula J, Fischer ES, Gray NS, Mitchison TJ. Tubulin Resists Degradation by Cereblon-Recruiting PROTACs. Cells. 2020 Apr 27; 9(5).
View in: PubMed
Manz TD, Sivakumaren SC, Ferguson FM, Zhang T, Yasgar A, Seo HS, Ficarro SB, Card JD, Shim H, Miduturu CV, Simeonov A, Shen M, Marto JA, Dhe-Paganon S, Hall MD, Cantley LC, Gray NS. Discovery and Structure-Activity Relationship Study of (Z)-5-Methylenethiazolidin-4-one Derivatives as Potent and Selective Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors. J Med Chem. 2020 05 14; 63(9):4880-4895.
View in: PubMed
Morita K, He S, Nowak RP, Wang J, Zimmerman MW, Fu C, Durbin AD, Martel MW, Prutsch N, Gray NS, Fischer ES, Look AT. Allosteric Activators of Protein Phosphatase 2A Display Broad Antitumor Activity Mediated by Dephosphorylation of MYBL2. Cell. 2020 Apr 30; 181(3):702-715.e20.
View in: PubMed
Ferguson FM, Nabet B, Raghavan S, Liu Y, Leggett AL, Kuljanin M, Kalekar RL, Yang A, He S, Wang J, Ng RWS, Sulahian R, Li L, Poulin EJ, Huang L, Koren J, Dieguez-Martinez N, Espinosa S, Zeng Z, Corona CR, Vasta JD, Ohi R, Sim T, Kim ND, Harshbarger W, Lizcano JM, Robers MB, Muthaswamy S, Lin CY, Look AT, Haigis KM, Mancias JD, Wolpin BM, Aguirre AJ, Hahn WC, Westover KD, Gray NS. Discovery of a selective inhibitor of doublecortin like kinase 1. Nat Chem Biol. 2020 06; 16(6):635-643.
View in: PubMed
Teng M, Ficarro SB, Yoon H, Che J, Zhou J, Fischer ES, Marto JA, Zhang T, Gray NS. Rationally Designed Covalent BCL6 Inhibitor That Targets a Tyrosine Residue in the Homodimer Interface. ACS Med Chem Lett. 2020 Jun 11; 11(6):1269-1273.
View in: PubMed
Santana-Codina N, Chandhoke AS, Yu Q, Malachowska B, Kuljanin M, Gikandi A, Stanczak M, Gableske S, Jedrychowski MP, Scott DA, Aguirre AJ, Fendler W, Gray NS, Mancias JD. Defining and Targeting Adaptations to Oncogenic KRASG12C Inhibition Using Quantitative Temporal Proteomics. Cell Rep. 2020 Mar 31; 30(13):4584-4599.e4.
View in: PubMed
Ogino A, Choi J, Lin M, Wilkens MK, Calles A, Xu M, Adeni AE, Chambers ES, Capelletti M, Butaney M, Gray NS, Gokhale PC, Palakurthi S, Kirschmeier P, Oxnard GR, Sholl LM, Jänne PA. Genomic and pathological heterogeneity in clinically diagnosed small cell lung cancer in never/light smokers identifies therapeutically targetable alterations. Mol Oncol. 2020 Mar 19.
View in: PubMed
Lochhead PA, Tucker JA, Tatum NJ, Wang J, Oxley D, Kidger AM, Johnson VP, Cassidy MA, Gray NS, Noble MEM, Cook SJ. Paradoxical activation of the protein kinase-transcription factor ERK5 by ERK5 kinase inhibitors. Nat Commun. 2020 03 13; 11(1):1383.
View in: PubMed
Sivakumaren SC, Shim H, Zhang T, Ferguson FM, Lundquist MR, Browne CM, Seo HS, Paddock MN, Manz TD, Jiang B, Hao MF, Krishnan P, Wang DG, Yang TJ, Kwiatkowski NP, Ficarro SB, Cunningham JM, Marto JA, Dhe-Paganon S, Cantley LC, Gray NS. Targeting the PI5P4K Lipid Kinase Family in Cancer Using Covalent Inhibitors. Cell Chem Biol. 2020 May 21; 27(5):525-537.e6.
View in: PubMed
Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS. Correction: An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem. 2020 Feb 28; 295(9):2886.
View in: PubMed
Xiao H, Jedrychowski MP, Schweppe DK, Huttlin EL, Yu Q, Heppner DE, Li J, Long J, Mills EL, Szpyt J, He Z, Du G, Garrity R, Reddy A, Vaites LP, Paulo JA, Zhang T, Gray NS, Gygi SP, Chouchani ET. A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging. Cell. 2020 03 05; 180(5):968-983.e24.
View in: PubMed
Liu J, Chen H, Ma L, He Z, Wang D, Liu Y, Lin Q, Zhang T, Gray N, Kaniskan HÜ, Jin J, Wei W. Light-induced control of protein destruction by opto-PROTAC. Sci Adv. 2020 02; 6(8):eaay5154.
View in: PubMed
Yang J, Meng C, Weisberg E, Case A, Lamberto I, Magin RS, Adamia S, Wang J, Gray N, Liu S, Stone R, Sattler M, Buhrlage S, Griffin JD. Inhibition of the deubiquitinase USP10 induces degradation of SYK. Br J Cancer. 2020 Apr; 122(8):1175-1184.
View in: PubMed
Munshi M, Liu X, Chen JG, Xu L, Tsakmaklis N, Demos MG, Kofides A, Guerrera ML, Jimenez C, Chan GG, Hunter ZR, Palomba ML, Argyropoulos KV, Meid K, Keezer A, Gustine J, Dubeau T, Castillo JJ, Patterson CJ, Wang J, Buhrlage SJ, Gray NS, Treon SP, Yang G. SYK is activated by mutated MYD88 and drives pro-survival signaling in MYD88 driven B-cell lymphomas. Blood Cancer J. 2020 01 31; 10(1):12.
View in: PubMed
Du G, Rao S, Gurbani D, Henning NJ, Jiang J, Che J, Yang A, Ficarro SB, Marto JA, Aguirre AJ, Sorger PK, Westover KD, Zhang T, Gray NS. Structure-Based Design of a Potent and Selective Covalent Inhibitor for SRC Kinase That Targets a P-Loop Cysteine. J Med Chem. 2020 02 27; 63(4):1624-1641.
View in: PubMed
Weisberg E, Meng C, Case AE, Tiv HL, Gokhale PC, Buhrlage SJ, Yang J, Liu X, Wang J, Gray N, Adamia S, Sattler M, Stone R, Griffin JD. Effects of the multi-kinase inhibitor midostaurin in combination with chemotherapy in models of acute myeloid leukaemia. J Cell Mol Med. 2020 Mar; 24(5):2968-2980.
View in: PubMed
Weisberg E, Meng C, Case AE, Tiv HL, Gokhale PC, Toure AA, Buhrlage S, Liu X, Wang J, Gray N, Stone R, Adamia S, Winer E, Sattler M, Griffin JD. The combination of FLT3 and SYK kinase inhibitors is toxic to leukaemia cells with CBL mutations. J Cell Mol Med. 2020 Feb; 24(3):2145-2156.
View in: PubMed
Kurppa KJ, Liu Y, To C, Zhang T, Fan M, Vajdi A, Knelson EH, Xie Y, Lim K, Cejas P, Portell A, Lizotte PH, Ficarro SB, Li S, Chen T, Haikala HM, Wang H, Bahcall M, Gao Y, Shalhout S, Boettcher S, Shin BH, Thai T, Wilkens MK, Tillgren ML, Mushajiang M, Xu M, Choi J, Bertram AA, Ebert BL, Beroukhim R, Bandopadhayay P, Awad MM, Gokhale PC, Kirschmeier PT, Marto JA, Camargo FD, Haq R, Paweletz CP, Wong KK, Barbie DA, Long HW, Gray NS, Jänne PA. Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway. Cancer Cell. 2020 01 13; 37(1):104-122.e12.
View in: PubMed
Kim JW, Berrios C, Kim M, Schade AE, Adelmant G, Yeerna H, Damato E, Iniguez AB, Florens L, Washburn MP, Stegmaier K, Gray NS, Tamayo P, Gjoerup O, Marto JA, DeCaprio J, Hahn WC. STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells. Elife. 2020 Jan 08; 9.
View in: PubMed
Groendyke BJ, Powell CE, Feru F, Gero TW, Li Z, Szabo H, Pang K, Feutrill J, Chen B, Li B, Gray NS, Scott DA. Benzopyrimidodiazepinone inhibitors of TNK2. Bioorg Med Chem Lett. 2020 02 15; 30(4):126948.
View in: PubMed
Tarumoto Y, Lin S, Wang J, Milazzo JP, Xu Y, Lu B, Yang Z, Wei Y, Polyanskaya S, Wunderlich M, Gray NS, Stegmaier K, Vakoc CR. Salt-inducible kinase inhibition suppresses acute myeloid leukemia progression in vivo. Blood. 2020 01 02; 135(1):56-70.
View in: PubMed
de Wispelaere M, Carocci M, Burri DJ, Neidermyer WJ, Olson CM, Roggenbach I, Liang Y, Wang J, Whelan SPJ, Gray NS, Yang PL. A broad-spectrum antiviral molecule, QL47, selectively inhibits eukaryotic translation. J Biol Chem. 2020 02 07; 295(6):1694-1703.
View in: PubMed
Zeng M, Xiong Y, Safaee N, Nowak RP, Donovan KA, Yuan CJ, Nabet B, Gero TW, Feru F, Li L, Gondi S, Ombelets LJ, Quan C, Jänne PA, Kostic M, Scott DA, Westover KD, Fischer ES, Gray NS. Exploring Targeted Degradation Strategy for Oncogenic KRASG12C. Cell Chem Biol. 2020 01 16; 27(1):19-31.e6.
View in: PubMed
Zhang H, Christensen CL, Dries R, Oser MG, Deng J, Diskin B, Li F, Pan Y, Zhang X, Yin Y, Papadopoulos E, Pyon V, Thakurdin C, Kwiatkowski N, Jani K, Rabin AR, Castro DM, Chen T, Silver H, Huang Q, Bulatovic M, Dowling CM, Sundberg B, Leggett A, Ranieri M, Han H, Li S, Yang A, Labbe KE, Almonte C, Sviderskiy VO, Quinn M, Donaghue J, Wang ES, Zhang T, He Z, Velcheti V, Hammerman PS, Freeman GJ, Bonneau R, Kaelin WG, Sutherland KD, Kersbergen A, Aguirre AJ, Yuan GC, Rothenberg E, Miller G, Gray NS, Wong KK. CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer. Cancer Cell. 2020 01 13; 37(1):37-54.e9.
View in: PubMed
You I, Erickson EC, Donovan KA, Eleuteri NA, Fischer ES, Gray NS, Toker A. Discovery of an AKT Degrader with Prolonged Inhibition of Downstream Signaling. Cell Chem Biol. 2020 01 16; 27(1):66-73.e7.
View in: PubMed
Chopra SS, Jenney A, Palmer A, Niepel M, Chung M, Mills C, Sivakumaren SC, Liu Q, Chen JY, Yapp C, Asara JM, Gray NS, Sorger PK. Torin2 Exploits Replication and Checkpoint Vulnerabilities to Cause Death of PI3K-Activated Triple-Negative Breast Cancer Cells. Cell Syst. 2020 01 22; 10(1):66-81.e11.
View in: PubMed
Li Z, Pinch BJ, Olson CM, Donovan KA, Nowak RP, Mills CE, Scott DA, Doctor ZM, Eleuteri NA, Chung M, Sorger PK, Fischer ES, Gray NS. Development and Characterization of a Wee1 Kinase Degrader. Cell Chem Biol. 2020 01 16; 27(1):57-65.e9.
View in: PubMed
Faust TB, Yoon H, Nowak RP, Donovan KA, Li Z, Cai Q, Eleuteri NA, Zhang T, Gray NS, Fischer ES. Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15. Nat Chem Biol. 2020 01; 16(1):7-14.
View in: PubMed
Manz TD, Sivakumaren SC, Yasgar A, Hall MD, Davis MI, Seo HS, Card JD, Ficarro SB, Shim H, Marto JA, Dhe-Paganon S, Sasaki AT, Boxer MB, Simeonov A, Cantley LC, Shen M, Zhang T, Ferguson FM, Gray NS. Structure-Activity Relationship Study of Covalent Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors. ACS Med Chem Lett. 2020 Mar 12; 11(3):346-352.
View in: PubMed
Lian W, Jang J, Potisopon S, Li PC, Rahmeh A, Wang J, Kwiatkowski NP, Gray NS, Yang PL. Correction to Discovery of Immunologically Inspired Small Molecules That Target the Viral Envelope Protein. ACS Infect Dis. 2019 Dec 13; 5(12):2176.
View in: PubMed
De Clercq DJH, Heppner DE, To C, Jang J, Park E, Yun CH, Mushajiang M, Shin BH, Gero TW, Scott DA, Jänne PA, Eck MJ, Gray NS. Discovery and Optimization of Dibenzodiazepinones as Allosteric Mutant-Selective EGFR Inhibitors. ACS Med Chem Lett. 2019 Nov 14; 10(11):1549-1553.
View in: PubMed
Menzl I, Zhang T, Berger-Becvar A, Grausenburger R, Heller G, Prchal-Murphy M, Edlinger L, Knab VM, Uras IZ, Grundschober E, Bauer K, Roth M, Skucha A, Liu Y, Hatcher JM, Liang Y, Kwiatkowski NP, Fux D, Hoelbl-Kovacic A, Kubicek S, Melo JV, Valent P, Weichhart T, Grebien F, Zuber J, Gray NS, Sexl V. A kinase-independent role for CDK8 in BCR-ABL1+ leukemia. Nat Commun. 2019 10 18; 10(1):4741.
View in: PubMed
Zhang T, Hatcher JM, Teng M, Gray NS, Kostic M. Recent Advances in Selective and Irreversible Covalent Ligand Development and Validation. Cell Chem Biol. 2019 11 21; 26(11):1486-1500.
View in: PubMed
Sulahian R, Kwon JJ, Walsh KH, Pailler E, Bosse TL, Thaker M, Almanza D, Dempster JM, Pan J, Piccioni F, Dumont N, Gonzalez A, Rennhack J, Nabet B, Bachman JA, Goodale A, Lee Y, Bagul M, Liao R, Navarro A, Yuan TL, Ng RWS, Raghavan S, Gray NS, Tsherniak A, Vazquez F, Root DE, Firestone AJ, Settleman J, Hahn WC, Aguirre AJ. Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers. Cell Rep. 2019 10 01; 29(1):118-134.e8.
View in: PubMed
Remillard D, Buckley DL, Seo HS, Ferguson FM, Dhe-Paganon S, Bradner JE, Gray NS. Dual Inhibition of TAF1 and BET Bromodomains from the BI-2536 Kinase Inhibitor Scaffold. ACS Med Chem Lett. 2019 Oct 10; 10(10):1443-1449.
View in: PubMed
Weisberg E, Meng C, Case A, Sattler M, Tiv HL, Gokhale PC, Buhrlage S, Wang J, Gray N, Stone R, Liu S, Bhagwat SV, Tiu RV, Adamia S, Griffin JD. Evaluation of ERK as a therapeutic target in acute myelogenous leukemia. Leukemia. 2020 02; 34(2):625-629.
View in: PubMed
Debruyne DN, Dries R, Sengupta S, Seruggia D, Gao Y, Sharma B, Huang H, Moreau L, McLane M, Day DS, Marco E, Chen T, Gray NS, Wong KK, Orkin SH, Yuan GC, Young RA, George RE. BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells. Nature. 2019 08; 572(7771):676-680.
View in: PubMed
de Wispelaere M, Du G, Donovan KA, Zhang T, Eleuteri NA, Yuan JC, Kalabathula J, Nowak RP, Fischer ES, Gray NS, Yang PL. Small molecule degraders of the hepatitis C virus protease reduce susceptibility to resistance mutations. Nat Commun. 2019 08 01; 10(1):3468.
View in: PubMed
Tang X, Drotar J, Li K, Clairmont CD, Brumm AS, Sullins AJ, Wu H, Liu XS, Wang J, Gray NS, Sur M, Jaenisch R. Pharmacological enhancement of KCC2 gene expression exerts therapeutic effects on human Rett syndrome neurons and Mecp2 mutant mice. Sci Transl Med. 2019 07 31; 11(503).
View in: PubMed
Weisberg E, Meng C, Case AE, Sattler M, Tiv HL, Gokhale PC, Buhrlage SJ, Liu X, Yang J, Wang J, Gray N, Stone RM, Adamia S, Dubreuil P, Letard S, Griffin JD. Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies. Br J Haematol. 2019 11; 187(4):488-501.
View in: PubMed
Ferguson FM, Doctor ZM, Ficarro SB, Marto JA, Kim ND, Sim T, Gray NS. Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14. Bioorg Med Chem Lett. 2019 08 01; 29(15):1985-1993.
View in: PubMed
Scott DA, Hatcher JM, Liu H, Fu M, Du G, Fontán L, Us I, Casalena G, Qiao Q, Wu H, Melnick A, Gray NS. Quinoline and thiazolopyridine allosteric inhibitors of MALT1. Bioorg Med Chem Lett. 2019 07 15; 29(14):1694-1698.
View in: PubMed
Rodon Ahnert J, Gray N, Mok T, Gainor J. What It Takes to Improve a First-Generation Inhibitor to a Second- or Third-Generation Small Molecule. Am Soc Clin Oncol Educ Book. 2019 Jan; 39:196-205.
View in: PubMed
Du L, Anderson A, Nguyen K, Ojeda SS, Ortiz-Rivera I, Nguyen TN, Zhang T, Kaoud TS, Gray NS, Dalby KN, Tsai KY. JNK2 Is Required for the Tumorigenic Properties of Melanoma Cells. ACS Chem Biol. 2019 07 19; 14(7):1426-1435.
View in: PubMed
To C, Jang J, Chen T, Park E, Mushajiang M, De Clercq DJH, Xu M, Wang S, Cameron MD, Heppner DE, Shin BH, Gero TW, Yang A, Dahlberg SE, Wong KK, Eck MJ, Gray NS, Jänne PA. Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor. Cancer Discov. 2019 07; 9(7):926-943.
View in: PubMed
Zhao X, Ren Y, Lawlor M, Shah BD, Park PMC, Lwin T, Wang X, Liu K, Wang M, Gao J, Li T, Xu M, Silva AS, Lee K, Zhang T, Koomen JM, Jiang H, Sudalagunta PR, Meads MB, Cheng F, Bi C, Fu K, Fan H, Dalton WS, Moscinski LC, Shain KH, Sotomayor EM, Wang GG, Gray NS, Cleveland JL, Qi J, Tao J. BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models. Cancer Cell. 2019 05 13; 35(5):752-766.e9.
View in: PubMed
Krajewska M, Dries R, Grassetti AV, Dust S, Gao Y, Huang H, Sharma B, Day DS, Kwiatkowski N, Pomaville M, Dodd O, Chipumuro E, Zhang T, Greenleaf AL, Yuan GC, Gray NS, Young RA, Geyer M, Gerber SA, George RE. CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation. Nat Commun. 2019 04 15; 10(1):1757.
View in: PubMed
Rao S, Gurbani D, Du G, Everley RA, Browne CM, Chaikuad A, Tan L, Schröder M, Gondi S, Ficarro SB, Sim T, Kim ND, Berberich MJ, Knapp S, Marto JA, Westover KD, Sorger PK, Gray NS. Leveraging Compound Promiscuity to Identify Targetable Cysteines within the Kinome. Cell Chem Biol. 2019 06 20; 26(6):818-829.e9.
View in: PubMed
Moret N, Clark NA, Hafner M, Wang Y, Lounkine E, Medvedovic M, Wang J, Gray N, Jenkins J, Sorger PK. Cheminformatics Tools for Analyzing and Designing Optimized Small-Molecule Collections and Libraries. Cell Chem Biol. 2019 05 16; 26(5):765-777.e3.
View in: PubMed
Hatcher JM, Du G, Fontán L, Us I, Qiao Q, Chennamadhavuni S, Shao J, Wu H, Melnick A, Gray NS, Scott DA. Peptide-based covalent inhibitors of MALT1 paracaspase. Bioorg Med Chem Lett. 2019 06 01; 29(11):1336-1339.
View in: PubMed
Jiang B, Wang ES, Donovan KA, Liang Y, Fischer ES, Zhang T, Gray NS. Development of Dual and Selective Degraders of Cyclin-Dependent Kinases 4 and 6. Angew Chem Int Ed Engl. 2019 05 06; 58(19):6321-6326.
View in: PubMed
Ferguson FM, Doctor ZM, Ficarro SB, Browne CM, Marto JA, Johnson JL, Yaron TM, Cantley LC, Kim ND, Sim T, Berberich MJ, Kalocsay M, Sorger PK, Gray NS. Discovery of Covalent CDK14 Inhibitors with Pan-TAIRE Family Specificity. Cell Chem Biol. 2019 06 20; 26(6):804-817.e12.
View in: PubMed
Silva MC, Ferguson FM, Cai Q, Donovan KA, Nandi G, Patnaik D, Zhang T, Huang HT, Lucente DE, Dickerson BC, Mitchison TJ, Fischer ES, Gray NS, Haggarty SJ. Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models. Elife. 2019 03 25; 8.
View in: PubMed
Olson CM, Liang Y, Leggett A, Park WD, Li L, Mills CE, Elsarrag SZ, Ficarro SB, Zhang T, Düster R, Geyer M, Sim T, Marto JA, Sorger PK, Westover KD, Lin CY, Kwiatkowski N, Gray NS. Development of a Selective CDK7 Covalent Inhibitor Reveals Predominant Cell-Cycle Phenotype. Cell Chem Biol. 2019 06 20; 26(6):792-803.e10.
View in: PubMed
Hsieh HHS, Agarwal S, Cholok DJ, Loder SJ, Kaneko K, Huber A, Chung MT, Ranganathan K, Habbouche J, Li J, Butts J, Reimer J, Kaura A, Drake J, Breuler C, Priest CR, Nguyen J, Brownley C, Peterson J, Ozgurel SU, Niknafs YS, Li S, Inagaki M, Scott G, Krebsbach PH, Longaker MT, Westover K, Gray N, Ninomiya-Tsuji J, Mishina Y, Levi B. Coordinating Tissue Regeneration Through Transforming Growth Factor-ß Activated Kinase 1 Inactivation and Reactivation. Stem Cells. 2019 06; 37(6):766-778.
View in: PubMed
Rao S, Du G, Hafner M, Subramanian K, Sorger PK, Gray NS. A multitargeted probe-based strategy to identify signaling vulnerabilities in cancers. J Biol Chem. 2019 05 24; 294(21):8664-8673.
View in: PubMed
Pitts J, Hsia CY, Lian W, Wang J, Pfeil MP, Kwiatkowski N, Li Z, Jang J, Gray NS, Yang PL. Identification of small molecule inhibitors targeting the Zika virus envelope protein. Antiviral Res. 2019 04; 164:147-153.
View in: PubMed
Wang L, Ferrao R, Li Q, Hatcher JM, Choi HG, Buhrlage SJ, Gray NS, Wu H. Conformational flexibility and inhibitor binding to unphosphorylated interleukin-1 receptor-associated kinase 4 (IRAK4). J Biol Chem. 2019 03 22; 294(12):4511-4519.
View in: PubMed
Sharifnia T, Wawer MJ, Chen T, Huang QY, Weir BA, Sizemore A, Lawlor MA, Goodale A, Cowley GS, Vazquez F, Ott CJ, Francis JM, Sassi S, Cogswell P, Sheppard HE, Zhang T, Gray NS, Clarke PA, Blagg J, Workman P, Sommer J, Hornicek F, Root DE, Hahn WC, Bradner JE, Wong KK, Clemons PA, Lin CY, Kotz JD, Schreiber SL. Small-molecule targeting of brachyury transcription factor addiction in chordoma. Nat Med. 2019 02; 25(2):292-300.
View in: PubMed
Li PC, Jang J, Hsia CY, Groomes PV, Lian W, de Wispelaere M, Pitts JD, Wang J, Kwiatkowski N, Gray NS, Yang PL. Small Molecules Targeting the Flavivirus E Protein with Broad-Spectrum Activity and Antiviral Efficacy in Vivo. ACS Infect Dis. 2019 03 08; 5(3):460-472.
View in: PubMed
Brand M, Jiang B, Bauer S, Donovan KA, Liang Y, Wang ES, Nowak RP, Yuan JC, Zhang T, Kwiatkowski N, Müller AC, Fischer ES, Gray NS, Winter GE. Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML. Cell Chem Biol. 2019 02 21; 26(2):300-306.e9.
View in: PubMed
Browne CM, Jiang B, Ficarro SB, Doctor ZM, Johnson JL, Card JD, Sivakumaren SC, Alexander WM, Yaron TM, Murphy CJ, Kwiatkowski NP, Zhang T, Cantley LC, Gray NS, Marto JA. A Chemoproteomic Strategy for Direct and Proteome-Wide Covalent Inhibitor Target-Site Identification. J Am Chem Soc. 2019 01 09; 141(1):191-203.
View in: PubMed
Dobrovolsky D, Wang ES, Morrow S, Leahy C, Faust T, Nowak RP, Donovan KA, Yang G, Li Z, Fischer ES, Treon SP, Weinstock DM, Gray NS. Bruton tyrosine kinase degradation as a therapeutic strategy for cancer. Blood. 2019 02 28; 133(9):952-961.
View in: PubMed
Brien GL, Remillard D, Shi J, Hemming ML, Chabon J, Wynne K, Dillon ET, Cagney G, Van Mierlo G, Baltissen MP, Vermeulen M, Qi J, Fröhling S, Gray NS, Bradner JE, Vakoc CR, Armstrong SA. Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma. Elife. 2018 11 15; 7.
View in: PubMed
Zeng M, Kwiatkowski NP, Zhang T, Nabet B, Xu M, Liang Y, Quan C, Wang J, Hao M, Palakurthi S, Zhou S, Zeng Q, Kirschmeier PT, Meghani K, Leggett AL, Qi J, Shapiro GI, Liu JF, Matulonis UA, Lin CY, Konstantinopoulos PA, Gray NS. Targeting MYC dependency in ovarian cancer through inhibition of CDK7 and CDK12/13. Elife. 2018 11 13; 7.
View in: PubMed
Michel BC, D’Avino AR, Cassel SH, Mashtalir N, McKenzie ZM, McBride MJ, Valencia AM, Zhou Q, Bocker M, Soares LMM, Pan J, Remillard DI, Lareau CA, Zullow HJ, Fortoul N, Gray NS, Bradner JE, Chan HM, Kadoch C. A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nat Cell Biol. 2018 12; 20(12):1410-1420.
View in: PubMed
Lizotte PH, Hong RL, Luster TA, Cavanaugh ME, Taus LJ, Wang S, Dhaneshwar A, Mayman N, Yang A, Kulkarni M, Badalucco L, Fitzpatrick E, Kao HF, Kuraguchi M, Bittinger M, Kirschmeier PT, Gray NS, Barbie DA, Jänne PA. A High-Throughput Immune-Oncology Screen Identifies EGFR Inhibitors as Potent Enhancers of Antigen-Specific Cytotoxic T-lymphocyte Tumor Cell Killing. Cancer Immunol Res. 2018 12; 6(12):1511-1523.
View in: PubMed
Tusa I, Cheloni G, Poteti M, Gozzini A, DeSouza NH, Shan Y, Deng X, Gray NS, Li S, Rovida E, Dello Sbarba P. Targeting the Extracellular Signal-Regulated Kinase 5 Pathway to Suppress Human Chronic Myeloid Leukemia Stem Cells. Stem Cell Reports. 2018 10 09; 11(4):929-943.
View in: PubMed
Cho H, Shin I, Ju E, Choi S, Hur W, Kim H, Hong E, Kim ND, Choi HG, Gray NS, Sim T. First SAR Study for Overriding NRAS Mutant Driven Acute Myeloid Leukemia. J Med Chem. 2018 09 27; 61(18):8353-8373.
View in: PubMed
Wang J, Erazo T, Ferguson FM, Buckley DL, Gomez N, Muñoz-Guardiola P, Diéguez-Martínez N, Deng X, Hao M, Massefski W, Fedorov O, Offei-Addo NK, Park PM, Dai L, DiBona A, Becht K, Kim ND, McKeown MR, Roberts JM, Zhang J, Sim T, Alessi DR, Bradner JE, Lizcano JM, Blacklow SC, Qi J, Xu X, Gray NS. Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinones as Inhibitors of Kinases and Bromodomains. ACS Chem Biol. 2018 09 21; 13(9):2438-2448.
View in: PubMed
Lian W, Jang J, Potisopon S, Li PC, Rahmeh A, Wang J, Kwiatkowski NP, Gray NS, Yang PL. Discovery of Immunologically Inspired Small Molecules That Target the Viral Envelope Protein. ACS Infect Dis. 2018 09 14; 4(9):1395-1406.
View in: PubMed
Czarna A, Wang J, Zelencova D, Liu Y, Deng X, Choi HG, Zhang T, Zhou W, Chang JW, Kildalsen H, Seternes OM, Gray NS, Engh RA, Rothweiler U. Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase (DYRK1A) Inhibitors. J Med Chem. 2018 09 13; 61(17):7560-7572.
View in: PubMed
Jang J, Son J, Park E, Kosaka T, Saxon JA, De Clercq DJH, Choi HG, Tanizaki J, Eck MJ, Jänne PA, Gray NS. Discovery of a Highly Potent and Broadly Effective Epidermal Growth Factor Receptor and HER2 Exon 20 Insertion Mutant Inhibitor. Angew Chem Int Ed Engl. 2018 09 03; 57(36):11629-11633.
View in: PubMed
Fontán L, Qiao Q, Hatcher JM, Casalena G, Us I, Teater M, Durant M, Du G, Xia M, Bilchuk N, Chennamadhavuni S, Palladino G, Inghirami G, Philippar U, Wu H, Scott DA, Gray NS, Melnick A. Specific covalent inhibition of MALT1 paracaspase suppresses B cell lymphoma growth. J Clin Invest. 2018 10 01; 128(10):4397-4412.
View in: PubMed
Chen S, Cai C, Sowalsky AG, Ye H, Ma F, Yuan X, Simon NI, Gray NS, Balk SP. BMX-Mediated Regulation of Multiple Tyrosine Kinases Contributes to Castration Resistance in Prostate Cancer. Cancer Res. 2018 09 15; 78(18):5203-5215.
View in: PubMed
Zhou W, Whiteley AT, de Oliveira Mann CC, Morehouse BR, Nowak RP, Fischer ES, Gray NS, Mekalanos JJ, Kranzusch PJ. Structure of the Human cGAS-DNA Complex Reveals Enhanced Control of Immune Surveillance. Cell. 2018 07 12; 174(2):300-311.e11.
View in: PubMed
Chao LH, Jang J, Johnson A, Nguyen A, Gray NS, Yang PL, Harrison SC. How small-molecule inhibitors of dengue-virus infection interfere with viral membrane fusion. Elife. 2018 07 12; 7.
View in: PubMed
Tusa I, Cheloni G, Poteti M, Gozzini A, Deng X, Gray NS, Li S, Dello Sbarba P, Rovida E. Targeting chronic myeloid leukemia stem cells with ERK5 pathway inhibitors. J Biol Regul Homeost Agents. 2018 Jul-Aug; 32(4 Suppl. 1):36.
View in: PubMed
de Wispelaere M, Lian W, Potisopon S, Li PC, Jang J, Ficarro SB, Clark MJ, Zhu X, Kaplan JB, Pitts JD, Wales TE, Wang J, Engen JR, Marto JA, Gray NS, Yang PL. Inhibition of Flaviviruses by Targeting a Conserved Pocket on the Viral Envelope Protein. Cell Chem Biol. 2018 08 16; 25(8):1006-1016.e8.
View in: PubMed
Nowak RP, DeAngelo SL, Buckley D, He Z, Donovan KA, An J, Safaee N, Jedrychowski MP, Ponthier CM, Ishoey M, Zhang T, Mancias JD, Gray NS, Bradner JE, Fischer ES. Plasticity in binding confers selectivity in ligand-induced protein degradation. Nat Chem Biol. 2018 07; 14(7):706-714.
View in: PubMed
Weir MC, Shu ST, Patel RK, Hellwig S, Chen L, Tan L, Gray NS, Smithgall TE. Selective Inhibition of the Myeloid Src-Family Kinase Fgr Potently Suppresses AML Cell Growth in Vitro and in Vivo. ACS Chem Biol. 2018 06 15; 13(6):1551-1559.
View in: PubMed
Powell CE, Gao Y, Tan L, Donovan KA, Nowak RP, Loehr A, Bahcall M, Fischer ES, Jänne PA, George RE, Gray NS. Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK). J Med Chem. 2018 05 10; 61(9):4249-4255.
View in: PubMed
Bockorny B, Rusan M, Chen W, Liao RG, Li Y, Piccioni F, Wang J, Tan L, Thorner AR, Li T, Zhang Y, Miao C, Ovesen T, Shapiro GI, Kwiatkowski DJ, Gray NS, Meyerson M, Hammerman PS, Bass AJ. RAS-MAPK Reactivation Facilitates Acquired Resistance in FGFR1-Amplified Lung Cancer and Underlies a Rationale for Upfront FGFR-MEK Blockade. . 2018 07; 17(7):1526-1539.
View in: PubMed
Nabet B, Gray NS. It Takes Two To Target: A Study in KRAS Dimerization. Biochemistry. 2018 04 24; 57(16):2289-2290.
View in: PubMed
Nabet B, Roberts JM, Buckley DL, Paulk J, Dastjerdi S, Yang A, Leggett AL, Erb MA, Lawlor MA, Souza A, Scott TG, Vittori S, Perry JA, Qi J, Winter GE, Wong KK, Gray NS, Bradner JE. The dTAG system for immediate and target-specific protein degradation. Nat Chem Biol. 2018 05; 14(5):431-441.
View in: PubMed
Hatcher JM, Wang ES, Johannessen L, Kwiatkowski N, Sim T, Gray NS. Development of Highly Potent and Selective Steroidal Inhibitors and Degraders of CDK8. ACS Med Chem Lett. 2018 Jun 14; 9(6):540-545.
View in: PubMed
Ferguson FM, Gray NS. Kinase inhibitors: the road ahead. Nat Rev Drug Discov. 2018 05; 17(5):353-377.
View in: PubMed
Wang Y, Li YM, Baitsch L, Huang A, Xiang Y, Tong H, Lako A, Von T, Choi C, Lim E, Min J, Li L, Stegmeier F, Schlegel R, Eck MJ, Gray NS, Mitchison TJ, Zhao JJ. Correction: MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. Elife. 2018 03 12; 7.
View in: PubMed
Giurisato E, Xu Q, Lonardi S, Telfer B, Russo I, Pearson A, Finegan KG, Wang W, Wang J, Gray NS, Vermi W, Xia Z, Tournier C. Myeloid ERK5 deficiency suppresses tumor growth by blocking protumor macrophage polarization via STAT3 inhibition. Proc Natl Acad Sci U S A. 2018 03 20; 115(12):E2801-E2810.
View in: PubMed
Gechijian LN, Buckley DL, Lawlor MA, Reyes JM, Paulk J, Ott CJ, Winter GE, Erb MA, Scott TG, Xu M, Seo HS, Dhe-Paganon S, Kwiatkowski NP, Perry JA, Qi J, Gray NS, Bradner JE. Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands. Nat Chem Biol. 2018 04; 14(4):405-412.
View in: PubMed
Chen JG, Liu X, Munshi M, Xu L, Tsakmaklis N, Demos MG, Kofides A, Guerrera ML, Chan GG, Patterson CJ, Meid K, Gustine J, Dubeau T, Severns P, Castillo JJ, Hunter ZR, Wang J, Buhrlage SJ, Gray NS, Treon SP, Yang G. BTKCys481Ser drives ibrutinib resistance via ERK1/2 and protects BTKwild-type MYD88-mutated cells by a paracrine mechanism. Blood. 2018 05 03; 131(18):2047-2059.
View in: PubMed
Tusa I, Gagliardi S, Tubita A, Pandolfi S, Urso C, Borgognoni L, Wang J, Deng X, Gray NS, Stecca B, Rovida E. ERK5 is activated by oncogenic BRAF and promotes melanoma growth. Oncogene. 2018 05; 37(19):2601-2614.
View in: PubMed
Hatcher JM, Wu G, Zeng C, Zhu J, Meng F, Patel S, Wang W, Ficarro SB, Leggett AL, Powell CE, Marto JA, Zhang K, Ki Ngo JC, Fu XD, Zhang T, Gray NS. SRPKIN-1: A Covalent SRPK1/2 Inhibitor that Potently Converts VEGF from Pro-angiogenic to Anti-angiogenic Isoform. Cell Chem Biol. 2018 04 19; 25(4):460-470.e6.
View in: PubMed
Jeselsohn R, Bergholz JS, Pun M, Cornwell M, Liu W, Nardone A, Xiao T, Li W, Qiu X, Buchwalter G, Feiglin A, Abell-Hart K, Fei T, Rao P, Long H, Kwiatkowski N, Zhang T, Gray N, Melchers D, Houtman R, Liu XS, Cohen O, Wagle N, Winer EP, Zhao J, Brown M. Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations. Cancer Cell. 2018 02 12; 33(2):173-186.e5.
View in: PubMed
Eliades P, Abraham BJ, Ji Z, Miller DM, Christensen CL, Kwiatkowski N, Kumar R, Njauw CN, Taylor M, Miao B, Zhang T, Wong KK, Gray NS, Young RA, Tsao H. High MITF Expression Is Associated with Super-Enhancers and Suppressed by CDK7 Inhibition in Melanoma. J Invest Dermatol. 2018 07; 138(7):1582-1590.
View in: PubMed
Zheng Y, Sethi R, Mangala LS, Taylor C, Goldsmith J, Wang M, Masuda K, Karaminejadranjbar M, Mannion D, Miranda F, Herrero-Gonzalez S, Hellner K, Chen F, Alsaadi A, Albukhari A, Fotso DC, Yau C, Jiang D, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, Knapp S, Gray NS, Campo L, Myers KA, Dhar S, Ferguson D, Bast RC, Sood AK, von Delft F, Ahmed AA. Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation. Nat Commun. 2018 02 02; 9(1):476.
View in: PubMed
Iniguez AB, Stolte B, Wang EJ, Conway AS, Alexe G, Dharia NV, Kwiatkowski N, Zhang T, Abraham BJ, Mora J, Kalev P, Leggett A, Chowdhury D, Benes CH, Young RA, Gray NS, Stegmaier K. EWS/FLI Confers Tumor Cell Synthetic Lethality to CDK12 Inhibition in Ewing Sarcoma. Cancer Cell. 2018 02 12; 33(2):202-216.e6.
View in: PubMed
Gao Y, Zhang T, Terai H, Ficarro SB, Kwiatkowski N, Hao MF, Sharma B, Christensen CL, Chipumuro E, Wong KK, Marto JA, Hammerman PS, Gray NS, George RE. Overcoming Resistance to the THZ Series of Covalent Transcriptional CDK Inhibitors. Cell Chem Biol. 2018 02 15; 25(2):135-142.e5.
View in: PubMed
Terai H, Kitajima S, Potter DS, Matsui Y, Quiceno LG, Chen T, Kim TJ, Rusan M, Thai TC, Piccioni F, Donovan KA, Kwiatkowski N, Hinohara K, Wei G, Gray NS, Fischer ES, Wong KK, Shimamura T, Letai A, Hammerman PS, Barbie DA. ER Stress Signaling Promotes the Survival of Cancer “Persister Cells” Tolerant to EGFR Tyrosine Kinase Inhibitors. Cancer Res. 2018 02 15; 78(4):1044-1057.
View in: PubMed
Olson CM, Jiang B, Erb MA, Liang Y, Doctor ZM, Zhang Z, Zhang T, Kwiatkowski N, Boukhali M, Green JL, Haas W, Nomanbhoy T, Fischer ES, Young RA, Bradner JE, Winter GE, Gray NS. Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation. Nat Chem Biol. 2018 02; 14(2):163-170.
View in: PubMed
Weintraub AS, Li CH, Zamudio AV, Sigova AA, Hannett NM, Day DS, Abraham BJ, Cohen MA, Nabet B, Buckley DL, Guo YE, Hnisz D, Jaenisch R, Bradner JE, Gray NS, Young RA. YY1 Is a Structural Regulator of Enhancer-Promoter Loops. Cell. 2017 Dec 14; 171(7):1573-1588.e28.
View in: PubMed
Wang L, Qiao Q, Ferrao R, Shen C, Hatcher JM, Buhrlage SJ, Gray NS, Wu H. Crystal structure of human IRAK1. Proc Natl Acad Sci U S A. 2017 12 19; 114(51):13507-13512.
View in: PubMed
Subramanian A, Narayan R, Corsello SM, Peck DD, Natoli TE, Lu X, Gould J, Davis JF, Tubelli AA, Asiedu JK, Lahr DL, Hirschman JE, Liu Z, Donahue M, Julian B, Khan M, Wadden D, Smith IC, Lam D, Liberzon A, Toder C, Bagul M, Orzechowski M, Enache OM, Piccioni F, Johnson SA, Lyons NJ, Berger AH, Shamji AF, Brooks AN, Vrcic A, Flynn C, Rosains J, Takeda DY, Hu R, Davison D, Lamb J, Ardlie K, Hogstrom L, Greenside P, Gray NS, Clemons PA, Silver S, Wu X, Zhao WN, Read-Button W, Wu X, Haggarty SJ, Ronco LV, Boehm JS, Schreiber SL, Doench JG, Bittker JA, Root DE, Wong B, Golub TR. A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles. Cell. 2017 Nov 30; 171(6):1437-1452.e17.
View in: PubMed
Keenan AB, Jenkins SL, Jagodnik KM, Koplev S, He E, Torre D, Wang Z, Dohlman AB, Silverstein MC, Lachmann A, Kuleshov MV, Ma’ayan A, Stathias V, Terryn R, Cooper D, Forlin M, Koleti A, Vidovic D, Chung C, Schürer SC, Vasiliauskas J, Pilarczyk M, Shamsaei B, Fazel M, Ren Y, Niu W, Clark NA, White S, Mahi N, Zhang L, Kouril M, Reichard JF, Sivaganesan S, Medvedovic M, Meller J, Koch RJ, Birtwistle MR, Iyengar R, Sobie EA, Azeloglu EU, Kaye J, Osterloh J, Haston K, Kalra J, Finkbiener S, Li J, Milani P, Adam M, Escalante-Chong R, Sachs K, Lenail A, Ramamoorthy D, Fraenkel E, Daigle G, Hussain U, Coye A, Rothstein J, Sareen D, Ornelas L, Banuelos M, Mandefro B, Ho R, Svendsen CN, Lim RG, Stocksdale J, Casale MS, Thompson TG, Wu J, Thompson LM, Dardov V, Venkatraman V, Matlock A, Van Eyk JE, Jaffe JD, Papanastasiou M, Subramanian A, Golub TR, Erickson SD, Fallahi-Sichani M, Hafner M, Gray NS, Lin JR, Mills CE, Muhlich JL, Niepel M, Shamu CE, Williams EH, Wrobel D, Sorger PK, Heiser LM, Gray JW, Korkola JE, Mills GB, LaBarge M, Feiler HS, Dane MA, Bucher E, Nederlof M, Sudar D, Gross S, Kilburn DF, Smith R, Devlin K, Margolis R, Derr L, Lee A, Pillai A. The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations. Cell Syst. 2018 01 24; 6(1):13-24.
View in: PubMed
Huang HT, Dobrovolsky D, Paulk J, Yang G, Weisberg EL, Doctor ZM, Buckley DL, Cho JH, Ko E, Jang J, Shi K, Choi HG, Griffin JD, Li Y, Treon SP, Fischer ES, Bradner JE, Tan L, Gray NS. A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader. Cell Chem Biol. 2018 01 18; 25(1):88-99.e6.
View in: PubMed
Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, Chhabra S, Huang W, Liu H, Aref AR, Ivanova E, Paweletz CP, Bowden M, Zhou CW, Herter-Sprie GS, Sorrentino JA, Bisi JE, Lizotte PH, Merlino AA, Quinn MM, Bufe LE, Yang A, Zhang Y, Zhang H, Gao P, Chen T, Cavanaugh ME, Rode AJ, Haines E, Roberts PJ, Strum JC, Richards WG, Lorch JH, Parangi S, Gunda V, Boland GM, Bueno R, Palakurthi S, Freeman GJ, Ritz J, Haining WN, Sharpless NE, Arthanari H, Shapiro GI, Barbie DA, Gray NS, Wong KK. CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation. Cancer Discov. 2018 02; 8(2):216-233.
View in: PubMed
Rusan M, Li K, Li Y, Christensen CL, Abraham BJ, Kwiatkowski N, Buczkowski KA, Bockorny B, Chen T, Li S, Rhee K, Zhang H, Chen W, Terai H, Tavares T, Leggett AL, Li T, Wang Y, Zhang T, Kim TJ, Hong SH, Poudel-Neupane N, Silkes M, Mudianto T, Tan L, Shimamura T, Meyerson M, Bass AJ, Watanabe H, Gray NS, Young RA, Wong KK, Hammerman PS. Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional Repression. Cancer Discov. 2018 01; 8(1):59-73.
View in: PubMed
Kalan S, Amat R, Schachter MM, Kwiatkowski N, Abraham BJ, Liang Y, Zhang T, Olson CM, Larochelle S, Young RA, Gray NS, Fisher RP. Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7 Inhibitors. Cell Rep. 2017 Oct 10; 21(2):467-481.
View in: PubMed
Wong RWJ, Ngoc PCT, Leong WZ, Yam AWY, Zhang T, Asamitsu K, Iida S, Okamoto T, Ueda R, Gray NS, Ishida T, Sanda T. Enhancer profiling identifies critical cancer genes and characterizes cell identity in adult T-cell leukemia. Blood. 2017 11 23; 130(21):2326-2338.
View in: PubMed
Weisberg EL, Schauer NJ, Yang J, Lamberto I, Doherty L, Bhatt S, Nonami A, Meng C, Letai A, Wright R, Tiv H, Gokhale PC, Ritorto MS, De Cesare V, Trost M, Christodoulou A, Christie A, Weinstock DM, Adamia S, Stone R, Chauhan D, Anderson KC, Seo HS, Dhe-Paganon S, Sattler M, Gray NS, Griffin JD, Buhrlage SJ. Inhibition of USP10 induces degradation of oncogenic FLT3. Nat Chem Biol. 2017 Dec; 13(12):1207-1215.
View in: PubMed
Huang HT, Seo HS, Zhang T, Wang Y, Jiang B, Li Q, Buckley DL, Nabet B, Roberts JM, Paulk J, Dastjerdi S, Winter GE, McLauchlan H, Moran J, Bradner JE, Eck MJ, Dhe-Paganon S, Zhao JJ, Gray NS. MELK is not necessary for the proliferation of basal-like breast cancer cells. Elife. 2017 09 19; 6.
View in: PubMed
Gilbert AS, Seoane PI, Sephton-Clark P, Bojarczuk A, Hotham R, Giurisato E, Sarhan AR, Hillen A, Velde GV, Gray NS, Alessi DR, Cunningham DL, Tournier C, Johnston SA, May RC. Vomocytosis of live pathogens from macrophages is regulated by the atypical MAP kinase ERK5. Sci Adv. 2017 08; 3(8):e1700898.
View in: PubMed
Johannessen L, Sundberg TB, O’Connell DJ, Kolde R, Berstler J, Billings KJ, Khor B, Seashore-Ludlow B, Fassl A, Russell CN, Latorre IJ, Jiang B, Graham DB, Perez JR, Sicinski P, Phillips AJ, Schreiber SL, Gray NS, Shamji AF, Xavier RJ. Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells. Nat Chem Biol. 2017 Oct; 13(10):1102-1108.
View in: PubMed
Ferguson FM, Doctor ZM, Chaikuad A, Sim T, Kim ND, Knapp S, Gray NS. Characterization of a highly selective inhibitor of the Aurora kinases. Bioorg Med Chem Lett. 2017 09 15; 27(18):4405-4408.
View in: PubMed
Zeng M, Lu J, Li L, Feru F, Quan C, Gero TW, Ficarro SB, Xiong Y, Ambrogio C, Paranal RM, Catalano M, Shao J, Wong KK, Marto JA, Fischer ES, Jänne PA, Scott DA, Westover KD, Gray NS. Potent and Selective Covalent Quinazoline Inhibitors of KRAS G12C. Cell Chem Biol. 2017 Aug 17; 24(8):1005-1016.e3.
View in: PubMed
Lu J, Harrison RA, Li L, Zeng M, Gondi S, Scott D, Gray NS, Engen JR, Westover KD. KRAS G12C Drug Development: Discrimination between Switch II Pocket Configurations Using Hydrogen/Deuterium-Exchange Mass Spectrometry. Structure. 2017 09 05; 25(9):1442-1448.e3.
View in: PubMed
Drewry DH, Wells CI, Andrews DM, Angell R, Al-Ali H, Axtman AD, Capuzzi SJ, Elkins JM, Ettmayer P, Frederiksen M, Gileadi O, Gray N, Hooper A, Knapp S, Laufer S, Luecking U, Michaelides M, Müller S, Muratov E, Denny RA, Saikatendu KS, Treiber DK, Zuercher WJ, Willson TM. Progress towards a public chemogenomic set for protein kinases and a call for contributions. PLoS One. 2017; 12(8):e0181585.
View in: PubMed
Liu Y, Li Y, Wang X, Liu F, Gao P, Quinn MM, Li F, Merlino AA, Benes C, Liu Q, Gray NS, Wong KK. Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma. Cancer Res. 2017 09 15; 77(18):5068-5076.
View in: PubMed
Weir MC, Hellwig S, Tan L, Liu Y, Gray NS, Smithgall TE. Dual inhibition of Fes and Flt3 tyrosine kinases potently inhibits Flt3-ITD+ AML cell growth. PLoS One. 2017; 12(7):e0181178.
View in: PubMed
Winter GE, Mayer A, Buckley DL, Erb MA, Roderick JE, Vittori S, Reyes JM, di Iulio J, Souza A, Ott CJ, Roberts JM, Zeid R, Scott TG, Paulk J, Lachance K, Olson CM, Dastjerdi S, Bauer S, Lin CY, Gray NS, Kelliher MA, Churchman LS, Bradner JE. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment. Mol Cell. 2017 Jul 06; 67(1):5-18.e19.
View in: PubMed
Mujahid N, Liang Y, Murakami R, Choi HG, Dobry AS, Wang J, Suita Y, Weng QY, Allouche J, Kemeny LV, Hermann AL, Roider EM, Gray NS, Fisher DE. A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin. Cell Rep. 2017 06 13; 19(11):2177-2184.
View in: PubMed
Wang B, Deng Y, Chen Y, Yu K, Wang A, Liang Q, Wang W, Chen C, Wu H, Hu C, Miao W, Hur W, Wang W, Hu Z, Weisberg EL, Wang J, Ren T, Wang Y, Gray NS, Liu Q, Liu J. Structure-activity relationship investigation for benzonaphthyridinone derivatives as novel potent Bruton’s tyrosine kinase (BTK) irreversible inhibitors. Eur J Med Chem. 2017 Sep 08; 137:545-557.
View in: PubMed
Vollmer S, Strickson S, Zhang T, Gray N, Lee KL, Rao VR, Cohen P. The mechanism of activation of IRAK1 and IRAK4 by interleukin-1 and Toll-like receptor agonists. Biochem J. 2017 06 06; 474(12):2027-2038.
View in: PubMed
Sun Y, Alberta JA, Pilarz C, Calligaris D, Chadwick EJ, Ramkissoon SH, Ramkissoon LA, Garcia VM, Mazzola E, Goumnerova L, Kane M, Yao Z, Kieran MW, Ligon KL, Hahn WC, Garraway LA, Rosen N, Gray NS, Agar NY, Buhrlage SJ, Segal RA, Stiles CD. A brain-penetrant RAF dimer antagonist for the noncanonical BRAF oncoprotein of pediatric low-grade astrocytomas. Neuro Oncol. 2017 06 01; 19(6):774-785.
View in: PubMed
Zwang Y, Jonas O, Chen C, Rinne ML, Doench JG, Piccioni F, Tan L, Huang HT, Wang J, Ham YJ, O’Connell J, Bhola P, Doshi M, Whitman M, Cima M, Letai A, Root DE, Langer RS, Gray N, Hahn WC. Synergistic interactions with PI3K inhibition that induce apoptosis. Elife. 2017 05 31; 6.
View in: PubMed
Williams CAC, Gray NS, Findlay GM. A Simple Method to Identify Kinases That Regulate Embryonic Stem Cell Pluripotency by High-throughput Inhibitor Screening. J Vis Exp. 2017 05 12; (123).
View in: PubMed
Manier S, Huynh D, Shen YJ, Zhou J, Yusufzai T, Salem KZ, Ebright RY, Shi J, Park J, Glavey SV, Devine WG, Liu CJ, Leleu X, Quesnel B, Roche-Lestienne C, Snyder JK, Brown LE, Gray N, Bradner J, Whitesell L, Porco JA, Ghobrial IM. Inhibiting the oncogenic translation program is an effective therapeutic strategy in multiple myeloma. Sci Transl Med. 2017 05 10; 9(389).
View in: PubMed
Jang J, Son JB, To C, Bahcall M, Kim SY, Kang SY, Mushajiang M, Lee Y, Jänne PA, Choi HG, Gray NS. Discovery of a potent dual ALK and EGFR T790M inhibitor. Eur J Med Chem. 2017 Aug 18; 136:497-510.
View in: PubMed
Wu H, Huang Q, Qi Z, Chen Y, Wang A, Chen C, Liang Q, Wang J, Chen W, Dong J, Yu K, Hu C, Wang W, Liu X, Deng Y, Wang L, Wang B, Li X, Gray NS, Liu J, Wei W, Liu Q. Irreversible inhibition of BTK kinase by a novel highly selective inhibitor CHMFL-BTK-11 suppresses inflammatory response in rheumatoid arthritis model. Sci Rep. 2017 03 28; 7(1):466.
View in: PubMed
Majkowska I, Shitomi Y, Ito N, Gray NS, Itoh Y. Discoidin domain receptor 2 mediates collagen-induced activation of membrane-type 1 matrix metalloproteinase in human fibroblasts. J Biol Chem. 2017 04 21; 292(16):6633-6643.
View in: PubMed
Wein MN, Liang Y, Goransson O, Sundberg TB, Wang J, Williams EA, O’Meara MJ, Govea N, Beqo B, Nishimori S, Nagano K, Brooks DJ, Martins JS, Corbin B, Anselmo A, Sadreyev R, Wu JY, Sakamoto K, Foretz M, Xavier RJ, Baron R, Bouxsein ML, Gardella TJ, Divieti-Pajevic P, Gray NS, Kronenberg HM. Corrigendum: SIKs control osteocyte responses to parathyroid hormone. Nat Commun. 2017 02 22; 8:14745.
View in: PubMed
Cayrol F, Praditsuktavorn P, Fernando TM, Kwiatkowski N, Marullo R, Calvo-Vidal MN, Phillip J, Pera B, Yang SN, Takpradit K, Roman L, Gaudiano M, Crescenzo R, Ruan J, Inghirami G, Zhang T, Cremaschi G, Gray NS, Cerchietti L. Corrigendum: THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors. Nat Commun. 2017 02 20; 8:14747.
View in: PubMed
Liang Y, de Wispelaere M, Carocci M, Liu Q, Wang J, Yang PL, Gray NS. Structure-Activity Relationship Study of QL47: A Broad-Spectrum Antiviral Agent. ACS Med Chem Lett. 2017 Mar 09; 8(3):344-349.
View in: PubMed
Cayrol F, Praditsuktavorn P, Fernando TM, Kwiatkowski N, Marullo R, Calvo-Vidal MN, Phillip J, Pera B, Yang SN, Takpradit K, Roman L, Gaudiano M, Crescenzo R, Ruan J, Inghirami G, Zhang T, Cremaschi G, Gray NS, Cerchietti L. THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors. Nat Commun. 2017 01 30; 8:14290.
View in: PubMed
Hatcher JM, Choi HG, Alessi DR, Gray NS. Small-Molecule Inhibitors of LRRK2. Adv Neurobiol. 2017; 14:241-264.
View in: PubMed
de Wispelaere M, Carocci M, Liang Y, Liu Q, Sun E, Vetter ML, Wang J, Gray NS, Yang PL. Discovery of host-targeted covalent inhibitors of dengue virus. Antiviral Res. 2017 Mar; 139:171-179.
View in: PubMed
Xie X, Kaoud TS, Edupuganti R, Zhang T, Kogawa T, Zhao Y, Chauhan GB, Giannoukos DN, Qi Y, Tripathy D, Wang J, Gray NS, Dalby KN, Bartholomeusz C, Ueno NT. c-Jun N-terminal kinase promotes stem cell phenotype in triple-negative breast cancer through upregulation of Notch1 via activation of c-Jun. Oncogene. 2017 05 04; 36(18):2599-2608.
View in: PubMed
Tan L, Gurbani D, Weisberg EL, Hunter JC, Li L, Jones DS, Ficarro SB, Mowafy S, Tam CP, Rao S, Du G, Griffin JD, Sorger PK, Marto JA, Westover KD, Gray NS. Structure-guided development of covalent TAK1 inhibitors. Bioorg Med Chem. 2017 02 01; 25(3):838-846.
View in: PubMed
Beelontally R, Wilkie GS, Lau B, Goodmaker CJ, Ho CMK, Swanson CM, Deng X, Wang J, Gray NS, Davison AJ, Strang BL. Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins. Antiviral Res. 2017 02; 138:61-67.
View in: PubMed
Tan L, Gurbani D, Weisberg EL, Jones DS, Rao S, Singer WD, Bernard FM, Mowafy S, Jenney A, Du G, Nonami A, Griffin JD, Lauffenburger DA, Westover KD, Sorger PK, Gray NS. Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. Bioorg Med Chem. 2017 02 15; 25(4):1320-1328.
View in: PubMed
Ficarro SB, Browne CM, Card JD, Alexander WM, Zhang T, Park E, McNally R, Dhe-Paganon S, Seo HS, Lamberto I, Eck MJ, Buhrlage SJ, Gray NS, Marto JA. Leveraging Gas-Phase Fragmentation Pathways for Improved Identification and Selective Detection of Targets Modified by Covalent Probes. Anal Chem. 2016 12 20; 88(24):12248-12254.
View in: PubMed
Xiong Y, Lu J, Hunter J, Li L, Scott D, Choi HG, Lim SM, Manandhar A, Gondi S, Sim T, Westover KD, Gray NS. Covalent Guanosine Mimetic Inhibitors of G12C KRAS. ACS Med Chem Lett. 2017 Jan 12; 8(1):61-66.
View in: PubMed
Shen Y, Park CS, Suppipat K, Mistretta TA, Puppi M, Horton TM, Rabin K, Gray NS, Meijerink JPP, Lacorazza HD. Inactivation of KLF4 promotes T-cell acute lymphoblastic leukemia and activates the MAP2K7 pathway. Leukemia. 2017 06; 31(6):1314-1324.
View in: PubMed
Hur W, Rosen H, Gray NS. A benzo[b]thiophene-based selective type 4 S1P receptor agonist. Bioorg Med Chem Lett. 2017 01 01; 27(1):1-5.
View in: PubMed
Wang A, Yan XE, Wu H, Wang W, Hu C, Chen C, Zhao Z, Zhao P, Li X, Wang L, Wang B, Ye Z, Wang J, Wang C, Zhang W, Gray NS, Weisberg EL, Chen L, Liu J, Yun CH, Liu Q. Ibrutinib targets mutant-EGFR kinase with a distinct binding conformation. Oncotarget. 2016 Oct 25; 7(43):69760-69769.
View in: PubMed
Wein MN, Liang Y, Goransson O, Sundberg TB, Wang J, Williams EA, O’Meara MJ, Govea N, Beqo B, Nishimori S, Nagano K, Brooks DJ, Martins JS, Corbin B, Anselmo A, Sadreyev R, Wu JY, Sakamoto K, Foretz M, Xavier RJ, Baron R, Bouxsein ML, Gardella TJ, Divieti-Pajevic P, Gray NS, Kronenberg HM. SIKs control osteocyte responses to parathyroid hormone. Nat Commun. 2016 10 19; 7:13176.
View in: PubMed
Zhang T, Kwiatkowski N, Olson CM, Dixon-Clarke SE, Abraham BJ, Greifenberg AK, Ficarro SB, Elkins JM, Liang Y, Hannett NM, Manz T, Hao M, Bartkowiak B, Greenleaf AL, Marto JA, Geyer M, Bullock AN, Young RA, Gray NS. Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors. Nat Chem Biol. 2016 10; 12(10):876-84.
View in: PubMed
Fan F, He Z, Kong LL, Chen Q, Yuan Q, Zhang S, Ye J, Liu H, Sun X, Geng J, Yuan L, Hong L, Xiao C, Zhang W, Sun X, Li Y, Wang P, Huang L, Wu X, Ji Z, Wu Q, Xia NS, Gray NS, Chen L, Yun CH, Deng X, Zhou D. Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration. Sci Transl Med. 2016 08 17; 8(352):352ra108.
View in: PubMed
Wang Y, Begley M, Li Q, Huang HT, Lako A, Eck MJ, Gray NS, Mitchison TJ, Cantley LC, Zhao JJ. Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival. Proc Natl Acad Sci U S A. 2016 08 30; 113(35):9810-5.
View in: PubMed
Williams CA, Fernandez-Alonso R, Wang J, Toth R, Gray NS, Findlay GM. Erk5 Is a Key Regulator of Naive-Primed Transition and Embryonic Stem Cell Identity. Cell Rep. 2016 08 16; 16(7):1820-8.
View in: PubMed
Ferguson FM, Ni J, Zhang T, Tesar B, Sim T, Kim ND, Deng X, Brown JR, Zhao JJ, Gray NS. Discovery of a Series of 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-ones as Selective PI3K-d/? Inhibitors. ACS Med Chem Lett. 2016 Oct 13; 7(10):908-912.
View in: PubMed
Miranda F, Mannion D, Liu S, Zheng Y, Mangala LS, Redondo C, Herrero-Gonzalez S, Xu R, Taylor C, Chedom DF, Karaminejadranjbar M, Albukhari A, Jiang D, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, Salah E, Abdul Azeez KR, Elkins JM, Campo L, Myers KA, Klotz D, Bivona S, Dhar S, Bast RC, Saya H, Choi HG, Gray NS, Fischer R, Kessler BM, Yau C, Sood AK, Motohara T, Knapp S, Ahmed AA. Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche. Cancer Cell. 2016 08 08; 30(2):273-289.
View in: PubMed
Pacold ME, Brimacombe KR, Chan SH, Rohde JM, Lewis CA, Swier LJ, Possemato R, Chen WW, Sullivan LB, Fiske BP, Cho S, Freinkman E, Birsoy K, Abu MR, Shaul YD, Liu CM, Zhou M, Koh MJ, Chung H, Davidson SM, Luengo A, Wang AQ, Xu X, Yasgar A, Liu L, Rai G, Westover KD, Heiden MG, Shen M, Gray NS, Boxer MB, Sabatini DM. Corrigendum: A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016 07 19; 12(8):656.
View in: PubMed
Iorio F, Knijnenburg TA, Vis DJ, Bignell GR, Menden MP, Schubert M, Aben N, Gonçalves E, Barthorpe S, Lightfoot H, Cokelaer T, Greninger P, van Dyk E, Chang H, de Silva H, Heyn H, Deng X, Egan RK, Liu Q, Mironenko T, Mitropoulos X, Richardson L, Wang J, Zhang T, Moran S, Sayols S, Soleimani M, Tamborero D, Lopez-Bigas N, Ross-Macdonald P, Esteller M, Gray NS, Haber DA, Stratton MR, Benes CH, Wessels LFA, Saez-Rodriguez J, McDermott U, Garnett MJ. A Landscape of Pharmacogenomic Interactions in Cancer. Cell. 2016 Jul 28; 166(3):740-754.
View in: PubMed
Chong CR, Bahcall M, Capelletti M, Kosaka T, Ercan D, Sim T, Sholl LM, Nishino M, Johnson BE, Gray NS, Jänne PA. Identification of Existing Drugs That Effectively Target NTRK1 and ROS1 Rearrangements in Lung Cancer. Clin Cancer Res. 2017 Jan 01; 23(1):204-213.
View in: PubMed
Brown WS, Tan L, Smith A, Gray NS, Wendt MK. Covalent Targeting of Fibroblast Growth Factor Receptor Inhibits Metastatic Breast Cancer. . 2016 09; 15(9):2096-106.
View in: PubMed
Lee S, Shang Y, Redmond SA, Urisman A, Tang AA, Li KH, Burlingame AL, Pak RA, Jovicic A, Gitler AD, Wang J, Gray NS, Seeley WW, Siddique T, Bigio EH, Lee VM, Trojanowski JQ, Chan JR, Huang EJ. Activation of HIPK2 Promotes ER Stress-Mediated Neurodegeneration in Amyotrophic Lateral Sclerosis. Neuron. 2016 07 06; 91(1):41-55.
View in: PubMed
Sundberg TB, Liang Y, Wu H, Choi HG, Kim ND, Sim T, Johannessen L, Petrone A, Khor B, Graham DB, Latorre IJ, Phillips AJ, Schreiber SL, Perez J, Shamji AF, Gray NS, Xavier RJ. Development of Chemical Probes for Investigation of Salt-Inducible Kinase Function in Vivo. ACS Chem Biol. 2016 08 19; 11(8):2105-11.
View in: PubMed
Matthews JM, Bhatt S, Patricelli MP, Nomanbhoy TK, Jiang X, Natkunam Y, Gentles AJ, Martinez E, Zhu D, Chapman JR, Cortizas E, Shyam R, Chinichian S, Advani R, Tan L, Zhang J, Choi HG, Tibshirani R, Buhrlage SJ, Gratzinger D, Verdun R, Gray NS, Lossos IS. Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma. Blood. 2016 07 14; 128(2):239-48.
View in: PubMed
Yang G, Buhrlage SJ, Tan L, Liu X, Chen J, Xu L, Tsakmaklis N, Chen JG, Patterson CJ, Brown JR, Castillo JJ, Zhang W, Zhang X, Liu S, Cohen P, Hunter ZR, Gray N, Treon SP. HCK is a survival determinant transactivated by mutated MYD88, and a direct target of ibrutinib. Blood. 2016 06 23; 127(25):3237-52.
View in: PubMed
Udayakumar D, Pandita RK, Horikoshi N, Liu Y, Liu Q, Wong KK, Hunt CR, Gray NS, Minna JD, Pandita TK, Westover KD. Torin2 Suppresses Ionizing Radiation-Induced DNA Damage Repair. Radiat Res. 2016 05; 185(5):527-38.
View in: PubMed
Pacold ME, Brimacombe KR, Chan SH, Rohde JM, Lewis CA, Swier LJ, Possemato R, Chen WW, Sullivan LB, Fiske BP, Cho S, Freinkman E, Birsoy K, Abu-Remaileh M, Shaul YD, Liu CM, Zhou M, Koh MJ, Chung H, Davidson SM, Luengo A, Wang AQ, Xu X, Yasgar A, Liu L, Rai G, Westover KD, Vander Heiden MG, Shen M, Gray NS, Boxer MB, Sabatini DM. A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate. Nat Chem Biol. 2016 06; 12(6):452-8.
View in: PubMed
Liu F, Wang J, Yang X, Li B, Wu H, Qi S, Chen C, Liu X, Yu K, Wang W, Zhao Z, Wang A, Chen Y, Wang L, Gray NS, Liu J, Zhang X, Liu Q. Discovery of a Highly Selective STK16 Kinase Inhibitor. ACS Chem Biol. 2016 06 17; 11(6):1537-43.
View in: PubMed
Clark MJ, Miduturu C, Schmidt AG, Zhu X, Pitts JD, Wang J, Potisopon S, Zhang J, Wojciechowski A, Hann Chu JJ, Gray NS, Yang PL. GNF-2 Inhibits Dengue Virus by Targeting Abl Kinases and the Viral E Protein. Cell Chem Biol. 2016 04 21; 23(4):443-52.
View in: PubMed
Liu X, Hunter ZR, Xu L, Chen J, Chen JG, Tsakmaklis N, Patterson CJ, Castillo JJ, Buhrlage S, Gray N, Treon SP, Yang G. Targeting Myddosome Assembly in Waldenstrom Macroglobulinaemia. Br J Haematol. 2017 06; 177(5):808-813.
View in: PubMed
Hatcher JM, Weisberg E, Sim T, Stone RM, Liu S, Griffin JD, Gray NS. Discovery of a Highly Potent and Selective Indenoindolone Type 1 Pan-FLT3 Inhibitor. ACS Med Chem Lett. 2016 May 12; 7(5):476-81.
View in: PubMed
Ho CM, Donovan-Banfield IZ, Tan L, Zhang T, Gray NS, Strang BL. Inhibition of IKKa by BAY61-3606 Reveals IKKa-Dependent Histone H3 Phosphorylation in Human Cytomegalovirus Infected Cells. PLoS One. 2016; 11(3):e0150339.
View in: PubMed
Westover KD, Jänne PA, Gray NS. Progress on Covalent Inhibition of KRAS(G12C). Cancer Discov. 2016 Mar; 6(3):233-4.
View in: PubMed
Nishikawa JL, Boeszoermenyi A, Vale-Silva LA, Torelli R, Posteraro B, Sohn YJ, Ji F, Gelev V, Sanglard D, Sanguinetti M, Sadreyev RI, Mukherjee G, Bhyravabhotla J, Buhrlage SJ, Gray NS, Wagner G, Näär AM, Arthanari H. Inhibiting fungal multidrug resistance by disrupting an activator-Mediator interaction. Nature. 2016 Feb 25; 530(7591):485-9.
View in: PubMed
Ye S, Zhang J, Shen J, Gao Y, Li Y, Choy E, Cote G, Harmon D, Mankin H, Gray NS, Hornicek FJ, Duan Z. NVP-TAE684 reverses multidrug resistance (MDR) in human osteosarcoma by inhibiting P-glycoprotein (PGP1) function. Br J Pharmacol. 2016 Feb; 173(3):613-26.
View in: PubMed
Amato KR, Wang S, Tan L, Hastings AK, Song W, Lovly CM, Meador CB, Ye F, Lu P, Balko JM, Colvin DC, Cates JM, Pao W, Gray NS, Chen J. EPHA2 Blockade Overcomes Acquired Resistance to EGFR Kinase Inhibitors in Lung Cancer. Cancer Res. 2016 Jan 15; 76(2):305-18.
View in: PubMed
Neel VA, Todorova K, Wang J, Kwon E, Kang M, Liu Q, Gray N, Lee SW, Mandinova A. Sustained Akt Activity Is Required to Maintain Cell Viability in Seborrheic Keratosis, a Benign Epithelial Tumor. J Invest Dermatol. 2016 Mar; 136(3):696-705.
View in: PubMed
Maxson JE, Abel ML, Wang J, Deng X, Reckel S, Luty SB, Sun H, Gorenstein J, Hughes SB, Bottomly D, Wilmot B, McWeeney SK, Radich J, Hantschel O, Middleton RE, Gray NS, Druker BJ, Tyner JW. Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis. Cancer Res. 2016 Jan 01; 76(1):127-38.
View in: PubMed
Debruyne DN, Bhatnagar N, Sharma B, Luther W, Moore NF, Cheung NK, Gray NS, George RE. ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is associated with AXL activation and induction of EMT. Oncogene. 2016 07 14; 35(28):3681-91.
View in: PubMed
Hatcher JM, Bahcall M, Choi HG, Gao Y, Sim T, George R, Jänne PA, Gray NS. Discovery of Inhibitors That Overcome the G1202R Anaplastic Lymphoma Kinase Resistance Mutation. J Med Chem. 2015 Dec 10; 58(23):9296-9308.
View in: PubMed
Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frederiksen M, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O’Hagan RC, Overington JP, Owen DR, Rosenberg SH, Ross R, Roth B, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, Zuercher WJ. Corrigendum: The promise and peril of chemical probes. Nat Chem Biol. 2015 Nov; 11(11):887.
View in: PubMed
Müller S, Chaikuad A, Gray NS, Knapp S. The ins and outs of selective kinase inhibitor development. Nat Chem Biol. 2015 Nov; 11(11):818-21.
View in: PubMed
Wu H, Wang A, Zhang W, Wang B, Chen C, Wang W, Hu C, Ye Z, Zhao Z, Wang L, Li X, Yu K, Liu J, Wu J, Yan XE, Zhao P, Wang J, Wang C, Weisberg EL, Gray NS, Yun CH, Liu J, Chen L, Liu Q. Ibrutinib selectively and irreversibly targets EGFR (L858R, Del19) mutant but is moderately resistant to EGFR (T790M) mutant NSCLC Cells. Oncotarget. 2015 Oct 13; 6(31):31313-22.
View in: PubMed
Galli GG, Carrara M, Yuan WC, Valdes-Quezada C, Gurung B, Pepe-Mooney B, Zhang T, Geeven G, Gray NS, de Laat W, Calogero RA, Camargo FD. YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers. Mol Cell. 2015 Oct 15; 60(2):328-37.
View in: PubMed
Terai H, Tan L, Beauchamp EM, Hatcher JM, Liu Q, Meyerson M, Gray NS, Hammerman PS. Characterization of DDR2 Inhibitors for the Treatment of DDR2 Mutated Nonsmall Cell Lung Cancer. ACS Chem Biol. 2015 Dec 18; 10(12):2687-96.
View in: PubMed
Wang Y, Zhang T, Kwiatkowski N, Abraham BJ, Lee TI, Xie S, Yuzugullu H, Von T, Li H, Lin Z, Stover DG, Lim E, Wang ZC, Iglehart JD, Young RA, Gray NS, Zhao JJ. CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell. 2015 Sep 24; 163(1):174-86.
View in: PubMed
Wilhelmsen K, Xu F, Farrar K, Tran A, Khakpour S, Sundar S, Prakash A, Wang J, Gray NS, Hellman J. Extracellular signal-regulated kinase 5 promotes acute cellular and systemic inflammation. Sci Signal. 2015 Aug 25; 8(391):ra86.
View in: PubMed
Tan L, Akahane K, McNally R, Reyskens KM, Ficarro SB, Liu S, Herter-Sprie GS, Koyama S, Pattison MJ, Labella K, Johannessen L, Akbay EA, Wong KK, Frank DA, Marto JA, Look TA, Arthur JS, Eck MJ, Gray NS. Development of Selective Covalent Janus Kinase 3 Inhibitors. J Med Chem. 2015 Aug 27; 58(16):6589-606.
View in: PubMed
Arrowsmith CH, Audia JE, Austin C, Baell J, Bennett J, Blagg J, Bountra C, Brennan PE, Brown PJ, Bunnage ME, Buser-Doepner C, Campbell RM, Carter AJ, Cohen P, Copeland RA, Cravatt B, Dahlin JL, Dhanak D, Edwards AM, Frederiksen M, Frye SV, Gray N, Grimshaw CE, Hepworth D, Howe T, Huber KV, Jin J, Knapp S, Kotz JD, Kruger RG, Lowe D, Mader MM, Marsden B, Mueller-Fahrnow A, Müller S, O’Hagan RC, Overington JP, Owen DR, Rosenberg SH, Roth B, Roth B, Ross R, Schapira M, Schreiber SL, Shoichet B, Sundström M, Superti-Furga G, Taunton J, Toledo-Sherman L, Walpole C, Walters MA, Willson TM, Workman P, Young RN, Zuercher WJ. The promise and peril of chemical probes. Nat Chem Biol. 2015 Aug; 11(8):536-41.
View in: PubMed
Wu H, Hu C, Wang A, Weisberg EL, Chen Y, Yun CH, Wang W, Liu Y, Liu X, Tian B, Wang J, Zhao Z, Liang Y, Li B, Wang L, Wang B, Chen C, Buhrlage SJ, Qi Z, Zou F, Nonami A, Li Y, Fernandes SM, Adamia S, Stone RM, Galinsky IA, Wang X, Yang G, Griffin JD, Brown JR, Eck MJ, Liu J, Gray NS, Liu Q. Discovery of a BTK/MNK dual inhibitor for lymphoma and leukemia. Leukemia. 2016 Jan; 30(1):173-81.
View in: PubMed
Rubinow KB, Wang S, den Hartigh LJ, Subramanian S, Morton GJ, Buaas FW, Lamont D, Gray N, Braun RE, Page ST. Hematopoietic androgen receptor deficiency promotes visceral fat deposition in male mice without impairing glucose homeostasis. Andrology. 2015 Jul; 3(4):787-96.
View in: PubMed
Moccia M, Liu Q, Guida T, Federico G, Brescia A, Zhao Z, Choi HG, Deng X, Tan L, Wang J, Billaud M, Gray NS, Carlomagno F, Santoro M. Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase. PLoS One. 2015; 10(6):e0128364.
View in: PubMed
Tricker EM, Xu C, Uddin S, Capelletti M, Ercan D, Ogino A, Pratilas CA, Rosen N, Gray NS, Wong KK, Jänne PA. Combined EGFR/MEK Inhibition Prevents the Emergence of Resistance in EGFR-Mutant Lung Cancer. Cancer Discov. 2015 Sep; 5(9):960-971.
View in: PubMed
Wang J, Gray NS. SnapShot: Kinase Inhibitors I. Mol Cell. 2015 May 21; 58(4):708.e1.
View in: PubMed
Wang J, Gray NS. SnapShot: Kinase Inhibitors II. Mol Cell. 2015 May 21; 58(4):710.e1.
View in: PubMed
Lim SM, Xie T, Westover KD, Ficarro SB, Tae HS, Gurbani D, Sim T, Marto JA, Jänne PA, Crews CM, Gray NS. Development of small molecules targeting the pseudokinase Her3. Bioorg Med Chem Lett. 2015 Aug 15; 25(16):3382-9.
View in: PubMed
Ercan D, Choi HG, Yun CH, Capelletti M, Xie T, Eck MJ, Gray NS, Jänne PA. EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors. Clin Cancer Res. 2015 Sep 01; 21(17):3913-23.
View in: PubMed
Malik N, Vollmer S, Nanda SK, Lopez-Pelaez M, Prescott A, Gray N, Cohen P. Suppression of interferon ß gene transcription by inhibitors of bromodomain and extra-terminal (BET) family members. Biochem J. 2015 Jun 15; 468(3):363-72.
View in: PubMed
Hatcher JM, Zhang J, Choi HG, Ito G, Alessi DR, Gray NS. Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor. ACS Med Chem Lett. 2015 May 14; 6(5):584-9.
View in: PubMed
Nonami A, Sattler M, Weisberg E, Liu Q, Zhang J, Patricelli MP, Christie AL, Saur AM, Kohl NE, Kung AL, Yoon H, Sim T, Gray NS, Griffin JD. Identification of novel therapeutic targets in acute leukemias with NRAS mutations using a pharmacologic approach. Blood. 2015 May 14; 125(20):3133-43.
View in: PubMed
Fallahi-Sichani M, Moerke NJ, Niepel M, Zhang T, Gray NS, Sorger PK. Systematic analysis of BRAF(V600E) melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis. Mol Syst Biol. 2015 Mar 26; 11(3):797.
View in: PubMed
Miao B, Ji Z, Tan L, Taylor M, Zhang J, Choi HG, Frederick DT, Kumar R, Wargo JA, Flaherty KT, Gray NS, Tsao H. EPHA2 is a mediator of vemurafenib resistance and a novel therapeutic target in melanoma. Cancer Discov. 2015 Mar; 5(3):274-87.
View in: PubMed
Christensen CL, Kwiatkowski N, Abraham BJ, Carretero J, Al-Shahrour F, Zhang T, Chipumuro E, Herter-Sprie GS, Akbay EA, Altabef A, Zhang J, Shimamura T, Capelletti M, Reibel JB, Cavanaugh JD, Gao P, Liu Y, Michaelsen SR, Poulsen HS, Aref AR, Barbie DA, Bradner JE, George RE, Gray NS, Young RA, Wong KK. Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell. 2014 Dec 08; 26(6):909-922.
View in: PubMed
Moroco JA, Baumgartner MP, Rust HL, Choi HG, Hur W, Gray NS, Camacho CJ, Smithgall TE. A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region. Chem Biol Drug Des. 2015 Aug; 86(2):144-55.
View in: PubMed
Chipumuro E, Marco E, Christensen CL, Kwiatkowski N, Zhang T, Hatheway CM, Abraham BJ, Sharma B, Yeung C, Altabef A, Perez-Atayde A, Wong KK, Yuan GC, Gray NS, Young RA, George RE. CDK7 inhibition suppresses super-enhancer-linked oncogenic transcription in MYCN-driven cancer. Cell. 2014 Nov 20; 159(5):1126-1139.
View in: PubMed
Umapathy G, El Wakil A, Witek B, Chesler L, Danielson L, Deng X, Gray NS, Johansson M, Kvarnbrink S, Ruuth K, Schönherr C, Palmer RH, Hallberg B. The kinase ALK stimulates the kinase ERK5 to promote the expression of the oncogene MYCN in neuroblastoma. Sci Signal. 2014 Oct 28; 7(349):ra102.
View in: PubMed
Huang Z, Tan L, Wang H, Liu Y, Blais S, Deng J, Neubert TA, Gray NS, Li X, Mohammadi M. DFG-out mode of inhibition by an irreversible type-1 inhibitor capable of overcoming gate-keeper mutations in FGF receptors. ACS Chem Biol. 2015 Jan 16; 10(1):299-309.
View in: PubMed
Tan L, Wang J, Tanizaki J, Huang Z, Aref AR, Rusan M, Zhu SJ, Zhang Y, Ercan D, Liao RG, Capelletti M, Zhou W, Hur W, Kim N, Sim T, Gaudet S, Barbie DA, Yeh JR, Yun CH, Hammerman PS, Mohammadi M, Jänne PA, Gray NS. Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci U S A. 2014 Nov 11; 111(45):E4869-77.
View in: PubMed
Xie T, Lim SM, Westover KD, Dodge ME, Ercan D, Ficarro SB, Udayakumar D, Gurbani D, Tae HS, Riddle SM, Sim T, Marto JA, Jänne PA, Crews CM, Gray NS. Pharmacological targeting of the pseudokinase Her3. Nat Chem Biol. 2014 Dec; 10(12):1006-12.
View in: PubMed
Lopez-Pelaez M, Lamont DJ, Peggie M, Shpiro N, Gray NS, Cohen P. Protein kinase IKKß-catalyzed phosphorylation of IRF5 at Ser462 induces its dimerization and nuclear translocation in myeloid cells. Proc Natl Acad Sci U S A. 2014 Dec 09; 111(49):17432-7.
View in: PubMed
Wagle N, Grabiner BC, Van Allen EM, Amin-Mansour A, Taylor-Weiner A, Rosenberg M, Gray N, Barletta JA, Guo Y, Swanson SJ, Ruan DT, Hanna GJ, Haddad RI, Getz G, Kwiatkowski DJ, Carter SL, Sabatini DM, Jänne PA, Garraway LA, Lorch JH. Response and acquired resistance to everolimus in anaplastic thyroid cancer. N Engl J Med. 2014 Oct 09; 371(15):1426-33.
View in: PubMed
Theunissen TW, Powell BE, Wang H, Mitalipova M, Faddah DA, Reddy J, Fan ZP, Maetzel D, Ganz K, Shi L, Lungjangwa T, Imsoonthornruksa S, Stelzer Y, Rangarajan S, D’Alessio A, Zhang J, Gao Q, Dawlaty MM, Young RA, Gray NS, Jaenisch R. Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency. Cell Stem Cell. 2014 Oct 02; 15(4):524-526.
View in: PubMed
Moore NF, Azarova AM, Bhatnagar N, Ross KN, Drake LE, Frumm S, Liu QS, Christie AL, Sanda T, Chesler L, Kung AL, Gray NS, Stegmaier K, George RE. Molecular rationale for the use of PI3K/AKT/mTOR pathway inhibitors in combination with crizotinib in ALK-mutated neuroblastoma. Oncotarget. 2014 Sep 30; 5(18):8737-49.
View in: PubMed
Duan Z, Zhang J, Ye S, Shen J, Choy E, Cote G, Harmon D, Mankin H, Hua Y, Zhang Y, Gray NS, Hornicek FJ. A-770041 reverses paclitaxel and doxorubicin resistance in osteosarcoma cells. BMC Cancer. 2014 Sep 19; 14:681.
View in: PubMed
Chaikuad A, Tacconi EM, Zimmer J, Liang Y, Gray NS, Tarsounas M, Knapp S. A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics. Nat Chem Biol. 2014 Oct; 10(10):853-60.
View in: PubMed
Weisberg E, Nonami A, Chen Z, Nelson E, Chen Y, Liu F, Cho H, Zhang J, Sattler M, Mitsiades C, Wong KK, Liu Q, Gray NS, Griffin JD. Upregulation of IGF1R by mutant RAS in leukemia and potentiation of RAS signaling inhibitors by small-molecule inhibition of IGF1R. Clin Cancer Res. 2014 Nov 01; 20(21):5483-95.
View in: PubMed
Rovida E, Di Maira G, Tusa I, Cannito S, Paternostro C, Navari N, Vivoli E, Deng X, Gray NS, Esparís-Ogando A, David E, Pandiella A, Dello Sbarba P, Parola M, Marra F. The mitogen-activated protein kinase ERK5 regulates the development and growth of hepatocellular carcinoma. Gut. 2015 Sep; 64(9):1454-65.
View in: PubMed
Calles A, Kwiatkowski N, Cammarata BK, Ercan D, Gray NS, Jänne PA. Tivantinib (ARQ 197) efficacy is independent of MET inhibition in non-small-cell lung cancer cell lines. Mol Oncol. 2015 Jan; 9(1):260-9.
View in: PubMed
Ritorto MS, Ewan R, Perez-Oliva AB, Knebel A, Buhrlage SJ, Wightman M, Kelly SM, Wood NT, Virdee S, Gray NS, Morrice NA, Alessi DR, Trost M. Screening of DUB activity and specificity by MALDI-TOF mass spectrometry. Nat Commun. 2014 Aug 27; 5:4763.
View in: PubMed
Theunissen TW, Powell BE, Wang H, Mitalipova M, Faddah DA, Reddy J, Fan ZP, Maetzel D, Ganz K, Shi L, Lungjangwa T, Imsoonthornruksa S, Stelzer Y, Rangarajan S, D’Alessio A, Zhang J, Gao Q, Dawlaty MM, Young RA, Gray NS, Jaenisch R. Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency. Cell Stem Cell. 2014 Oct 02; 15(4):523.
View in: PubMed
Sundberg TB, Choi HG, Song JH, Russell CN, Hussain MM, Graham DB, Khor B, Gagnon J, O’Connell DJ, Narayan K, Dancík V, Perez JR, Reinecker HC, Gray NS, Schreiber SL, Xavier RJ, Shamji AF. Small-molecule screening identifies inhibition of salt-inducible kinases as a therapeutic strategy to enhance immunoregulatory functions of dendritic cells. Proc Natl Acad Sci U S A. 2014 Aug 26; 111(34):12468-73.
View in: PubMed
Derbyshire ER, Zuzarte-Luís V, Magalhães AD, Kato N, Sanschagrin PC, Wang J, Zhou W, Miduturu CV, Mazitschek R, Sliz P, Mota MM, Gray NS, Clardy J. Chemical interrogation of the malaria kinome. Chembiochem. 2014 Sep 05; 15(13):1920-30.
View in: PubMed
Patel K, Foretz M, Marion A, Campbell DG, Gourlay R, Boudaba N, Tournier E, Titchenell P, Peggie M, Deak M, Wan M, Kaestner KH, Göransson O, Viollet B, Gray NS, Birnbaum MJ, Sutherland C, Sakamoto K. The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver. Nat Commun. 2014 Aug 04; 5:4535.
View in: PubMed
Tan L, Nomanbhoy T, Gurbani D, Patricelli M, Hunter J, Geng J, Herhaus L, Zhang J, Pauls E, Ham Y, Choi HG, Xie T, Deng X, Buhrlage SJ, Sim T, Cohen P, Sapkota G, Westover KD, Gray NS. Discovery of type II inhibitors of TGFß-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). J Med Chem. 2015 Jan 08; 58(1):183-96.
View in: PubMed
Theunissen TW, Powell BE, Wang H, Mitalipova M, Faddah DA, Reddy J, Fan ZP, Maetzel D, Ganz K, Shi L, Lungjangwa T, Imsoonthornruksa S, Stelzer Y, Rangarajan S, D’Alessio A, Zhang J, Gao Q, Dawlaty MM, Young RA, Gray NS, Jaenisch R. Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell. 2014 10 02; 15(4):471-487.
View in: PubMed
Murchie P, Raja EA, Brewster DH, Campbell NC, Ritchie LD, Robertson R, Samuel L, Gray N, Lee AJ. Time from first presentation in primary care to treatment of symptomatic colorectal cancer: effect on disease stage and survival. Br J Cancer. 2014 Jul 29; 111(3):461-9.
View in: PubMed
Kwiatkowski N, Zhang T, Rahl PB, Abraham BJ, Reddy J, Ficarro SB, Dastur A, Amzallag A, Ramaswamy S, Tesar B, Jenkins CE, Hannett NM, McMillin D, Sanda T, Sim T, Kim ND, Look T, Mitsiades CS, Weng AP, Brown JR, Benes CH, Marto JA, Young RA, Gray NS. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 2014 Jul 31; 511(7511):616-20.
View in: PubMed
Wang J, Mikse O, Liao RG, Li Y, Tan L, Janne PA, Gray NS, Wong KK, Hammerman PS. Ligand-associated ERBB2/3 activation confers acquired resistance to FGFR inhibition in FGFR3-dependent cancer cells. Oncogene. 2015 Apr 23; 34(17):2167-77.
View in: PubMed
Hunter JC, Gurbani D, Ficarro SB, Carrasco MA, Lim SM, Choi HG, Xie T, Marto JA, Chen Z, Gray NS, Westover KD. In situ selectivity profiling and crystal structure of SML-8-73-1, an active site inhibitor of oncogenic K-Ras G12C. Proc Natl Acad Sci U S A. 2014 Jun 17; 111(24):8895-900.
View in: PubMed
Wang Y, Lee YM, Baitsch L, Huang A, Xiang Y, Tong H, Lako A, Von T, Choi C, Lim E, Min J, Li L, Stegmeier F, Schlegel R, Eck MJ, Gray NS, Mitchison TJ, Zhao JJ. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells. Elife. 2014 May 20; 3:e01763.
View in: PubMed
Vetter ML, Zhang Z, Liu S, Wang J, Cho H, Zhang J, Zhang W, Gray NS, Yang PL. Fluorescent visualization of Src by using dasatinib-BODIPY. Chembiochem. 2014 Jun 16; 15(9):1317-24.
View in: PubMed
Weisberg E, Nonami A, Chen Z, Liu F, Zhang J, Sattler M, Nelson E, Cowens K, Christie AL, Mitsiades C, Wong KK, Liu Q, Gray N, Griffin JD. Identification of Wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies. Leukemia. 2015 Jan; 29(1):27-37.
View in: PubMed
Zhao Z, Wu H, Wang L, Liu Y, Knapp S, Liu Q, Gray NS. Exploration of type II binding mode: A privileged approach for kinase inhibitor focused drug discovery? ACS Chem Biol. 2014 Jun 20; 9(6):1230-41.
View in: PubMed
Canning P, Tan L, Chu K, Lee SW, Gray NS, Bullock AN. Structural mechanisms determining inhibition of the collagen receptor DDR1 by selective and multi-targeted type II kinase inhibitors. J Mol Biol. 2014 Jun 26; 426(13):2457-70.
View in: PubMed
Amato KR, Wang S, Hastings AK, Youngblood VM, Santapuram PR, Chen H, Cates JM, Colvin DC, Ye F, Brantley-Sieders DM, Cook RS, Tan L, Gray NS, Chen J. Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC. J Clin Invest. 2014 May; 124(5):2037-49.
View in: PubMed
Codeluppi S, Fernandez-Zafra T, Sandor K, Kjell J, Liu Q, Abrams M, Olson L, Gray NS, Svensson CI, Uhlén P. Interleukin-6 secretion by astrocytes is dynamically regulated by PI3K-mTOR-calcium signaling. PLoS One. 2014; 9(3):e92649.
View in: PubMed
Decker S, Finter J, Forde AJ, Kissel S, Schwaller J, Mack TS, Kuhn A, Gray N, Follo M, Jumaa H, Burger M, Zirlik K, Pfeifer D, Miduturu CV, Eibel H, Veelken H, Dierks C. PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3) and CXCR4-mediated microenvironmental interactions (PIM1). . 2014 May; 13(5):1231-45.
View in: PubMed
Wu H, Wang W, Liu F, Weisberg EL, Tian B, Chen Y, Li B, Wang A, Wang B, Zhao Z, McMillin DW, Hu C, Li H, Wang J, Liang Y, Buhrlage SJ, Liang J, Liu J, Yang G, Brown JR, Treon SP, Mitsiades CS, Griffin JD, Liu Q, Gray NS. Discovery of a potent, covalent BTK inhibitor for B-cell lymphoma. ACS Chem Biol. 2014 May 16; 9(5):1086-91.
View in: PubMed
Kim HG, Tan L, Weisberg EL, Liu F, Canning P, Choi HG, Ezell S, Zhao Z, Wu H, Wang J, Mandinova A, Bullock AN, Liu Q, Lee SW, Gray NS. Correction to Discovery of a Potent and Selective DDR1 Receptor Tyrosine Kinase Inhibitor. ACS Chem Biol. 2014 Mar 21; 9(3):840.
View in: PubMed
Ficarro SB, Biagi JM, Wang J, Scotcher J, Koleva RI, Card JD, Adelmant G, He H, Askenazi M, Marshall AG, Young NL, Gray NS, Marto JA. Protected amine labels: a versatile molecular scaffold for multiplexed nominal mass and sub-Da isotopologue quantitative proteomic reagents. J Am Soc Mass Spectrom. 2014 Apr; 25(4):636-50.
View in: PubMed
Gray NS, Fabbro D. Discovery of allosteric BCR-ABL inhibitors from phenotypic screen to clinical candidate. Methods Enzymol. 2014; 548:173-88.
View in: PubMed
Banerjee S, Buhrlage SJ, Huang HT, Deng X, Zhou W, Wang J, Traynor R, Prescott AR, Alessi DR, Gray NS. Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases. Biochem J. 2014 Jan 01; 457(1):215-25.
View in: PubMed
Beauchamp EM, Woods BA, Dulak AM, Tan L, Xu C, Gray NS, Bass AJ, Wong KK, Meyerson M, Hammerman PS. Acquired resistance to dasatinib in lung cancer cell lines conferred by DDR2 gatekeeper mutation and NF1 loss. . 2014 Feb; 13(2):475-82.
View in: PubMed
Lim SM, Westover KD, Ficarro SB, Harrison RA, Choi HG, Pacold ME, Carrasco M, Hunter J, Kim ND, Xie T, Sim T, Jänne PA, Meyerson M, Marto JA, Engen JR, Gray NS. Therapeutic targeting of oncogenic K-Ras by a covalent catalytic site inhibitor. Angew Chem Int Ed Engl. 2014 Jan 03; 53(1):199-204.
View in: PubMed
Deng X, Elkins JM, Zhang J, Yang Q, Erazo T, Gomez N, Choi HG, Wang J, Dzamko N, Lee JD, Sim T, Kim N, Alessi DR, Lizcano JM, Knapp S, Gray NS. Structural determinants for ERK5 (MAPK7) and leucine rich repeat kinase 2 activities of benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-ones. Eur J Med Chem. 2013; 70:758-67.
View in: PubMed
Mistry H, Hsieh G, Buhrlage SJ, Huang M, Park E, Cuny GD, Galinsky I, Stone RM, Gray NS, D’Andrea AD, Parmar K. Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells. . 2013 Dec; 12(12):2651-62.
View in: PubMed
Angell HK, Gray N, Womack C, Pritchard DI, Wilkinson RW, Cumberbatch M. Digital pattern recognition-based image analysis quantifies immune infiltrates in distinct tissue regions of colorectal cancer and identifies a metastatic phenotype. Br J Cancer. 2013 Sep 17; 109(6):1618-24.
View in: PubMed
Kim HG, Tan L, Weisberg EL, Liu F, Canning P, Choi HG, Ezell SA, Wu H, Zhao Z, Wang J, Mandinova A, Griffin JD, Bullock AN, Liu Q, Lee SW, Gray NS. Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor. ACS Chem Biol. 2013 Oct 18; 8(10):2145-50.
View in: PubMed
Tannous BA, Kerami M, Van der Stoop PM, Kwiatkowski N, Wang J, Zhou W, Kessler AF, Lewandrowski G, Hiddingh L, Sol N, Lagerweij T, Wedekind L, Niers JM, Barazas M, Nilsson RJ, Geerts D, De Witt Hamer PC, Hagemann C, Vandertop WP, Van Tellingen O, Noske DP, Gray NS, Würdinger T. Effects of the selective MPS1 inhibitor MPS1-IN-3 on glioblastoma sensitivity to antimitotic drugs. J Natl Cancer Inst. 2013 Sep 04; 105(17):1322-31.
View in: PubMed
Kang SA, Pacold ME, Cervantes CL, Lim D, Lou HJ, Ottina K, Gray NS, Turk BE, Yaffe MB, Sabatini DM. mTORC1 phosphorylation sites encode their sensitivity to starvation and rapamycin. Science. 2013 Jul 26; 341(6144):1236566.
View in: PubMed
Yang G, Zhou Y, Liu X, Xu L, Cao Y, Manning RJ, Patterson CJ, Buhrlage SJ, Gray N, Tai YT, Anderson KC, Hunter ZR, Treon SP. A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. Blood. 2013 Aug 15; 122(7):1222-32.
View in: PubMed
Taipale M, Krykbaeva I, Whitesell L, Santagata S, Zhang J, Liu Q, Gray NS, Lindquist S. Chaperones as thermodynamic sensors of drug-target interactions reveal kinase inhibitor specificities in living cells. Nat Biotechnol. 2013 Jul; 31(7):630-7.
View in: PubMed
Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013 Jul 25; 56(14):5675-90.
View in: PubMed
Liao RG, Jung J, Tchaicha J, Wilkerson MD, Sivachenko A, Beauchamp EM, Liu Q, Pugh TJ, Pedamallu CS, Hayes DN, Gray NS, Getz G, Wong KK, Haddad RI, Meyerson M, Hammerman PS. Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung squamous cell carcinoma. Cancer Res. 2013 Aug 15; 73(16):5195-205.
View in: PubMed
Liu Y, Marks K, Cowley GS, Carretero J, Liu Q, Nieland TJ, Xu C, Cohoon TJ, Gao P, Zhang Y, Chen Z, Altabef AB, Tchaicha JH, Wang X, Choe S, Driggers EM, Zhang J, Bailey ST, Sharpless NE, Hayes DN, Patel NM, Janne PA, Bardeesy N, Engelman JA, Manning BD, Shaw RJ, Asara JM, Scully R, Kimmelman A, Byers LA, Gibbons DL, Wistuba II, Heymach JV, Kwiatkowski DJ, Kim WY, Kung AL, Gray NS, Root DE, Cantley LC, Wong KK. Metabolic and functional genomic studies identify deoxythymidylate kinase as a target in LKB1-mutant lung cancer. Cancer Discov. 2013 Aug; 3(8):870-9.
View in: PubMed
Elkins JM, Wang J, Deng X, Pattison MJ, Arthur JS, Erazo T, Gomez N, Lizcano JM, Gray NS, Knapp S. X-ray crystal structure of ERK5 (MAPK7) in complex with a specific inhibitor. J Med Chem. 2013 Jun 13; 56(11):4413-21.
View in: PubMed
Liu F, Zhang X, Weisberg E, Chen S, Hur W, Wu H, Zhao Z, Wang W, Mao M, Cai C, Simon NI, Sanda T, Wang J, Look AT, Griffin JD, Balk SP, Liu Q, Gray NS. Discovery of a selective irreversible BMX inhibitor for prostate cancer. ACS Chem Biol. 2013 Jul 19; 8(7):1423-8.
View in: PubMed
Guo Y, Chekaluk Y, Zhang J, Du J, Gray NS, Wu CL, Kwiatkowski DJ. TSC1 involvement in bladder cancer: diverse effects and therapeutic implications. J Pathol. 2013 May; 230(1):17-27.
View in: PubMed
Jain R, Jain D, Liu Q, Bartosinska B, Wang J, Schumann D, Kauschke SG, Eickelmann P, Piemonti L, Gray NS, Lammert E. Pharmacological inhibition of Eph receptors enhances glucose-stimulated insulin secretion from mouse and human pancreatic islets. Diabetologia. 2013 Jun; 56(6):1350-5.
View in: PubMed
Sanda T, Tyner JW, Gutierrez A, Ngo VN, Glover J, Chang BH, Yost A, Ma W, Fleischman AG, Zhou W, Yang Y, Kleppe M, Ahn Y, Tatarek J, Kelliher MA, Neuberg DS, Levine RL, Moriggl R, Müller M, Gray NS, Jamieson CH, Weng AP, Staudt LM, Druker BJ, Look AT. TYK2-STAT1-BCL2 pathway dependence in T-cell acute lymphoblastic leukemia. Cancer Discov. 2013 May; 3(5):564-77.
View in: PubMed
Liu Q, Xu C, Kirubakaran S, Zhang X, Hur W, Liu Y, Kwiatkowski NP, Wang J, Westover KD, Gao P, Ercan D, Niepel M, Thoreen CC, Kang SA, Patricelli MP, Wang Y, Tupper T, Altabef A, Kawamura H, Held KD, Chou DM, Elledge SJ, Janne PA, Wong KK, Sabatini DM, Gray NS. Characterization of Torin2, an ATP-competitive inhibitor of mTOR, ATM, and ATR. Cancer Res. 2013 Apr 15; 73(8):2574-86.
View in: PubMed
Weisberg E, Liu Q, Zhang X, Nelson E, Sattler M, Liu F, Nicolais M, Zhang J, Mitsiades C, Smith RW, Stone R, Galinsky I, Nonami A, Griffin JD, Gray N. Selective Akt inhibitors synergize with tyrosine kinase inhibitors and effectively override stroma-associated cytoprotection of mutant FLT3-positive AML cells. PLoS One. 2013; 8(2):e56473.
View in: PubMed
Liu Q, Sabnis Y, Zhao Z, Zhang T, Buhrlage SJ, Jones LH, Gray NS. Developing irreversible inhibitors of the protein kinase cysteinome. Chem Biol. 2013 Feb 21; 20(2):146-59.
View in: PubMed
Pan S, Gray NS, Gao W, Mi Y, Fan Y, Wang X, Tuntland T, Che J, Lefebvre S, Chen Y, Chu A, Hinterding K, Gardin A, End P, Heining P, Bruns C, Cooke NG, Nuesslein-Hildesheim B. Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator. ACS Med Chem Lett. 2013 Mar 14; 4(3):333-7.
View in: PubMed
Knapp S, Arruda P, Blagg J, Burley S, Drewry DH, Edwards A, Fabbro D, Gillespie P, Gray NS, Kuster B, Lackey KE, Mazzafera P, Tomkinson NC, Willson TM, Workman P, Zuercher WJ. A public-private partnership to unlock the untargeted kinome. Nat Chem Biol. 2013 Jan; 9(1):3-6.
View in: PubMed
Cortot AB, Repellin CE, Shimamura T, Capelletti M, Zejnullahu K, Ercan D, Christensen JG, Wong KK, Gray NS, Jänne PA. Resistance to irreversible EGF receptor tyrosine kinase inhibitors through a multistep mechanism involving the IGF1R pathway. Cancer Res. 2013 Jan 15; 73(2):834-43.
View in: PubMed
Deng X, Choi HG, Buhrlage SJ, Gray NS. Leucine-rich repeat kinase 2 inhibitors: a patent review (2006 – 2011). Expert Opin Ther Pat. 2012 Dec; 22(12):1415-26.
View in: PubMed
Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, Groenewegen A, Vitaliti A, Sing T, Luttringer O, Yang J, Gardin A, Wang N, Crumb WJ, Saltzman M, Rosenberg M, Wallström E. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol. 2012 Nov; 167(5):1035-47.
View in: PubMed
Clark K, MacKenzie KF, Petkevicius K, Kristariyanto Y, Zhang J, Choi HG, Peggie M, Plater L, Pedrioli PG, McIver E, Gray NS, Arthur JS, Cohen P. Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Natl Acad Sci U S A. 2012 Oct 16; 109(42):16986-91.
View in: PubMed
Zhang Z, Kwiatkowski N, Zeng H, Lim SM, Gray NS, Zhang W, Yang PL. Leveraging kinase inhibitors to develop small molecule tools for imaging kinases by fluorescence microscopy. Mol Biosyst. 2012 Oct; 8(10):2523-6.
View in: PubMed
Ercan D, Xu C, Yanagita M, Monast CS, Pratilas CA, Montero J, Butaney M, Shimamura T, Sholl L, Ivanova EV, Tadi M, Rogers A, Repellin C, Capelletti M, Maertens O, Goetz EM, Letai A, Garraway LA, Lazzara MJ, Rosen N, Gray NS, Wong KK, Jänne PA. Reactivation of ERK signaling causes resistance to EGFR kinase inhibitors. Cancer Discov. 2012 Oct; 2(10):934-47.
View in: PubMed
Yang Q, Liao L, Deng X, Chen R, Gray NS, Yates JR, Lee JD. BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2 interaction. Oncogene. 2013 Jun 27; 32(26):3156-64.
View in: PubMed
Lau KS, Zhang T, Kendall KR, Lauffenburger D, Gray NS, Haigis KM. BAY61-3606 affects the viability of colon cancer cells in a genotype-directed manner. PLoS One. 2012; 7(7):e41343.
View in: PubMed
Cheng CK, Gustafson WC, Charron E, Houseman BT, Zunder E, Goga A, Gray NS, Pollok B, Oakes SA, James CD, Shokat KM, Weiss WA, Fan QW. Dual blockade of lipid and cyclin-dependent kinases induces synthetic lethality in malignant glioma. Proc Natl Acad Sci U S A. 2012 Jul 31; 109(31):12722-7.
View in: PubMed
Duan Z, Zhang J, Choy E, Harmon D, Liu X, Nielsen P, Mankin H, Gray NS, Hornicek FJ. Systematic kinome shRNA screening identifies CDK11 (PITSLRE) kinase expression is critical for osteosarcoma cell growth and proliferation. Clin Cancer Res. 2012 Sep 01; 18(17):4580-8.
View in: PubMed
Berry T, Luther W, Bhatnagar N, Jamin Y, Poon E, Sanda T, Pei D, Sharma B, Vetharoy WR, Hallsworth A, Ahmad Z, Barker K, Moreau L, Webber H, Wang W, Liu Q, Perez-Atayde A, Rodig S, Cheung NK, Raynaud F, Hallberg B, Robinson SP, Gray NS, Pearson AD, Eccles SA, Chesler L, George RE. The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell. 2012 Jul 10; 22(1):117-30.
View in: PubMed
Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P, Choi HG, Deng X, Zhang J, Alessi DR, Gray NS. GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent-N-arylbenzamide LRRK2 kinase inhibitor. Bioorg Med Chem Lett. 2012 Sep 01; 22(17):5625-9.
View in: PubMed
Choi HG, Zhang J, Weisberg E, Griffin JD, Sim T, Gray NS. Development of ‘DFG-out’ inhibitors of gatekeeper mutant kinases. Bioorg Med Chem Lett. 2012 Aug 15; 22(16):5297-302.
View in: PubMed
Dzamko N, Inesta-Vaquera F, Zhang J, Xie C, Cai H, Arthur S, Tan L, Choi H, Gray N, Cohen P, Pedrioli P, Clark K, Alessi DR. The IkappaB kinase family phosphorylates the Parkinson’s disease kinase LRRK2 at Ser935 and Ser910 during Toll-like receptor signaling. PLoS One. 2012; 7(6):e39132.
View in: PubMed
Choi HG, Zhang J, Deng X, Hatcher JM, Patricelli MP, Zhao Z, Alessi DR, Gray NS. Brain Penetrant LRRK2 Inhibitor. ACS Med Chem Lett. 2012 Aug 09; 3(8):658-662.
View in: PubMed
Deng X, Zhou W, Weisberg E, Wang J, Zhang J, Sasaki T, Nelson E, Griffin JD, Jänne PA, Gray NS. An amino-indazole scaffold with spectrum selective kinase inhibition of FLT3, PDGFRa and kit. Bioorg Med Chem Lett. 2012 Jul 15; 22(14):4579-84.
View in: PubMed
Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature. 2012 May 02; 485(7396):109-13.
View in: PubMed
Hellwig S, Miduturu CV, Kanda S, Zhang J, Filippakopoulos P, Salah E, Deng X, Choi HG, Zhou W, Hur W, Knapp S, Gray NS, Smithgall TE. Small-molecule inhibitors of the c-Fes protein-tyrosine kinase. Chem Biol. 2012 Apr 20; 19(4):529-40.
View in: PubMed
Liu Q, Ren T, Fresques T, Oppliger W, Niles BJ, Hur W, Sabatini DM, Hall MN, Powers T, Gray NS. Selective ATP-competitive inhibitors of TOR suppress rapamycin-insensitive function of TORC2 in Saccharomyces cerevisiae. ACS Chem Biol. 2012 Jun 15; 7(6):982-7.
View in: PubMed
Ni J, Liu Q, Xie S, Carlson C, Von T, Vogel K, Riddle S, Benes C, Eck M, Roberts T, Gray N, Zhao J. Functional characterization of an isoform-selective inhibitor of PI3K-p110ß as a potential anticancer agent. Cancer Discov. 2012 May; 2(5):425-33.
View in: PubMed
Weisberg E, Liu Q, Nelson E, Kung AL, Christie AL, Bronson R, Sattler M, Sanda T, Zhao Z, Hur W, Mitsiades C, Smith R, Daley JF, Stone R, Galinsky I, Griffin JD, Gray N. Using combination therapy to override stromal-mediated chemoresistance in mutant FLT3-positive AML: synergism between FLT3 inhibitors, dasatinib/multi-targeted inhibitors and JAK inhibitors. Leukemia. 2012 Oct; 26(10):2233-44.
View in: PubMed
Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, Greninger P, Thompson IR, Luo X, Soares J, Liu Q, Iorio F, Surdez D, Chen L, Milano RJ, Bignell GR, Tam AT, Davies H, Stevenson JA, Barthorpe S, Lutz SR, Kogera F, Lawrence K, McLaren-Douglas A, Mitropoulos X, Mironenko T, Thi H, Richardson L, Zhou W, Jewitt F, Zhang T, O’Brien P, Boisvert JL, Price S, Hur W, Yang W, Deng X, Butler A, Choi HG, Chang JW, Baselga J, Stamenkovic I, Engelman JA, Sharma SV, Delattre O, Saez-Rodriguez J, Gray NS, Settleman J, Futreal PA, Haber DA, Stratton MR, Ramaswamy S, McDermott U, Benes CH. Systematic identification of genomic markers of drug sensitivity in cancer cells. Nature. 2012 Mar 28; 483(7391):570-5.
View in: PubMed
Zhang J, Deng X, Choi HG, Alessi DR, Gray NS. Characterization of TAE684 as a potent LRRK2 kinase inhibitor. Bioorg Med Chem Lett. 2012 Mar 01; 22(5):1864-9.
View in: PubMed
Zhang T, Inesta-Vaquera F, Niepel M, Zhang J, Ficarro SB, Machleidt T, Xie T, Marto JA, Kim N, Sim T, Laughlin JD, Park H, LoGrasso PV, Patricelli M, Nomanbhoy TK, Sorger PK, Alessi DR, Gray NS. Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27; 19(1):140-54.
View in: PubMed
Liu Q, Kirubakaran S, Hur W, Niepel M, Westover K, Thoreen CC, Wang J, Ni J, Patricelli MP, Vogel K, Riddle S, Waller DL, Traynor R, Sanda T, Zhao Z, Kang SA, Zhao J, Look AT, Sorger PK, Sabatini DM, Gray NS. Kinome-wide selectivity profiling of ATP-competitive mammalian target of rapamycin (mTOR) inhibitors and characterization of their binding kinetics. J Biol Chem. 2012 Mar 23; 287(13):9742-52.
View in: PubMed
Liu Q, Kang SA, Thoreen CC, Hur W, Wang J, Chang JW, Markhard A, Zhang J, Sim T, Sabatini DM, Gray NS. Development of ATP-competitive mTOR inhibitors. Methods Mol Biol. 2012; 821:447-60.
View in: PubMed
Kwiatkowski N, Deng X, Wang J, Tan L, Villa F, Santaguida S, Huang HC, Mitchison T, Musacchio A, Gray N. Selective aurora kinase inhibitors identified using a taxol-induced checkpoint sensitivity screen. ACS Chem Biol. 2012 Jan 20; 7(1):185-96.
View in: PubMed
Liu P, Cheng H, Santiago S, Raeder M, Zhang F, Isabella A, Yang J, Semaan DJ, Chen C, Fox EA, Gray NS, Monahan J, Schlegel R, Beroukhim R, Mills GB, Zhao JJ. Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms. Nat Med. 2011 Aug 07; 17(9):1116-20.
View in: PubMed
Miduturu CV, Deng X, Kwiatkowski N, Yang W, Brault L, Filippakopoulos P, Chung E, Yang Q, Schwaller J, Knapp S, King RW, Lee JD, Herrgard S, Zarrinkar P, Gray NS. High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors. Chem Biol. 2011 Jul 29; 18(7):868-79.
View in: PubMed
Sasaki T, Koivunen J, Ogino A, Yanagita M, Nikiforow S, Zheng W, Lathan C, Marcoux JP, Du J, Okuda K, Capelletti M, Shimamura T, Ercan D, Stumpfova M, Xiao Y, Weremowicz S, Butaney M, Heon S, Wilner K, Christensen JG, Eck MJ, Wong KK, Lindeman N, Gray NS, Rodig SJ, Jänne PA. A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 2011 Sep 15; 71(18):6051-60.
View in: PubMed
McMillin DW, Delmore J, Negri J, Ooi M, Klippel S, Miduturu CV, Gray NS, Richardson PG, Anderson KC, Kung AL, Mitsiades CS. Microenvironmental influence on pre-clinical activity of polo-like kinase inhibition in multiple myeloma: implications for clinical translation. PLoS One. 2011; 6(7):e20226.
View in: PubMed
Patricelli MP, Nomanbhoy TK, Wu J, Brown H, Zhou D, Zhang J, Jagannathan S, Aban A, Okerberg E, Herring C, Nordin B, Weissig H, Yang Q, Lee JD, Gray NS, Kozarich JW. In situ kinase profiling reveals functionally relevant properties of native kinases. Chem Biol. 2011 Jun 24; 18(6):699-710.
View in: PubMed
Hsu PP, Kang SA, Rameseder J, Zhang Y, Ottina KA, Lim D, Peterson TR, Choi Y, Gray NS, Yaffe MB, Marto JA, Sabatini DM. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science. 2011 Jun 10; 332(6035):1317-22.
View in: PubMed
Dutt A, Ramos AH, Hammerman PS, Mermel C, Cho J, Sharifnia T, Chande A, Tanaka KE, Stransky N, Greulich H, Gray NS, Meyerson M. Inhibitor-sensitive FGFR1 amplification in human non-small cell lung cancer. PLoS One. 2011; 6(6):e20351.
View in: PubMed
Hammerman PS, Sos ML, Ramos AH, Xu C, Dutt A, Zhou W, Brace LE, Woods BA, Lin W, Zhang J, Deng X, Lim SM, Heynck S, Peifer M, Simard JR, Lawrence MS, Onofrio RC, Salvesen HB, Seidel D, Zander T, Heuckmann JM, Soltermann A, Moch H, Koker M, Leenders F, Gabler F, Querings S, Ansén S, Brambilla E, Brambilla C, Lorimier P, Brustugun OT, Helland A, Petersen I, Clement JH, Groen H, Timens W, Sietsma H, Stoelben E, Wolf J, Beer DG, Tsao MS, Hanna M, Hatton C, Eck MJ, Janne PA, Johnson BE, Winckler W, Greulich H, Bass AJ, Cho J, Rauh D, Gray NS, Wong KK, Haura EB, Thomas RK, Meyerson M. Mutations in the DDR2 kinase gene identify a novel therapeutic target in squamous cell lung cancer. Cancer Discov. 2011 Jun; 1(1):78-89.
View in: PubMed
Liu Q, Wang J, Kang SA, Thoreen CC, Hur W, Choi HG, Waller DL, Sim T, Sabatini DM, Gray NS. Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability. Bioorg Med Chem Lett. 2011 Jul 01; 21(13):4036-40.
View in: PubMed
Haber DA, Gray NS, Baselga J. The evolving war on cancer. Cell. 2011 Apr 01; 145(1):19-24.
View in: PubMed
Deng X, Wang J, Zhang J, Sim T, Kim ND, Sasaki T, Luther W, George RE, Jänne PA, Gray NS. Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors. ACS Med Chem Lett. 2011 May 12; 2(5):379-384.
View in: PubMed
Deng X, Dzamko N, Prescott A, Davies P, Liu Q, Yang Q, Lee JD, Patricelli MP, Nomanbhoy TK, Alessi DR, Gray NS. Characterization of a selective inhibitor of the Parkinson’s disease kinase LRRK2. Nat Chem Biol. 2011 Apr; 7(4):203-5.
View in: PubMed
Liu Q, Wang J, Kang SA, Thoreen CC, Hur W, Ahmed T, Sabatini DM, Gray NS. Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer. J Med Chem. 2011 Mar 10; 54(5):1473-80.
View in: PubMed
Deng X, Yang Q, Kwiatkowski N, Sim T, McDermott U, Settleman JE, Lee JD, Gray NS. Discovery of a benzo[e]pyrimido-[5,4-b][1,4]diazepin-6(11H)-one as a Potent and Selective Inhibitor of Big MAP Kinase 1. ACS Med Chem Lett. 2011 Mar 10; 2(3):195-200.
View in: PubMed
Iacob RE, Zhang J, Gray NS, Engen JR. Allosteric interactions between the myristate- and ATP-site of the Abl kinase. PLoS One. 2011 Jan 10; 6(1):e15929.
View in: PubMed
Hur W, Gray NS. Small molecule modulators of antioxidant response pathway. Curr Opin Chem Biol. 2011 Feb; 15(1):162-73.
View in: PubMed
Sharp L, Cotton S, Gray N, Avis M, Russell I, Walker L, Waugh N, Whynes D, Woolley C, Thornton A, Smart L, Cruickshank M, Little J. Long-term psychosocial impact of alternative management policies in women with low-grade abnormal cervical cytology referred for colposcopy: a randomised controlled trial. Br J Cancer. 2011 Jan 18; 104(2):255-64.
View in: PubMed
Zhou W, Ercan D, Jänne PA, Gray NS. Discovery of selective irreversible inhibitors for EGFR-T790M. Bioorg Med Chem Lett. 2011 Jan 15; 21(2):638-43.
View in: PubMed
Sasaki T, Okuda K, Zheng W, Butrynski J, Capelletti M, Wang L, Gray NS, Wilner K, Christensen JG, Demetri G, Shapiro GI, Rodig SJ, Eck MJ, Jänne PA. The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers. Cancer Res. 2010 Dec 15; 70(24):10038-43.
View in: PubMed
Chen Z, Sasaki T, Tan X, Carretero J, Shimamura T, Li D, Xu C, Wang Y, Adelmant GO, Capelletti M, Lee HJ, Rodig SJ, Borgman C, Park SI, Kim HR, Padera R, Marto JA, Gray NS, Kung AL, Shapiro GI, Jänne PA, Wong KK. Inhibition of ALK, PI3K/MEK, and HSP90 in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene. Cancer Res. 2010 Dec 01; 70(23):9827-36.
View in: PubMed
Liu Q, Chang JW, Wang J, Kang SA, Thoreen CC, Markhard A, Hur W, Zhang J, Sim T, Sabatini DM, Gray NS. Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer. J Med Chem. 2010 Oct 14; 53(19):7146-55.
View in: PubMed
Deng X, Okram B, Ding Q, Zhang J, Choi Y, Adrián FJ, Wojciechowski A, Zhang G, Che J, Bursulaya B, Cowan-Jacob SW, Rummel G, Sim T, Gray NS. Expanding the diversity of allosteric bcr-abl inhibitors. J Med Chem. 2010 Oct 14; 53(19):6934-46.
View in: PubMed
Yang Q, Deng X, Lu B, Cameron M, Fearns C, Patricelli MP, Yates JR, Gray NS, Lee JD. Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell. 2010 Sep 14; 18(3):258-67.
View in: PubMed
Weisberg E, Choi HG, Barrett R, Zhou W, Zhang J, Ray A, Nelson EA, Jiang J, Moreno D, Stone R, Galinsky I, Fox E, Adamia S, Kung AL, Gray NS, Griffin JD. Discovery and characterization of novel mutant FLT3 kinase inhibitors. . 2010 Sep; 9(9):2468-77.
View in: PubMed
Choi HG, Ren P, Adrian F, Sun F, Lee HS, Wang X, Ding Q, Zhang G, Xie Y, Zhang J, Liu Y, Tuntland T, Warmuth M, Manley PW, Mestan J, Gray NS, Sim T. A type-II kinase inhibitor capable of inhibiting the T315I “gatekeeper” mutant of Bcr-Abl. J Med Chem. 2010 Aug 12; 53(15):5439-48.
View in: PubMed
Deng X, Nagle A, Wu T, Sakata T, Henson K, Chen Z, Kuhen K, Plouffe D, Winzeler E, Adrian F, Tuntland T, Chang J, Simerson S, Howard S, Ek J, Isbell J, Tully DC, Chatterjee AK, Gray NS. Discovery of novel 1H-imidazol-2-yl-pyrimidine-4,6-diamines as potential antimalarials. Bioorg Med Chem Lett. 2010 Jul 15; 20(14):4027-31.
View in: PubMed
Hur W, Sun Z, Jiang T, Mason DE, Peters EC, Zhang DD, Luesch H, Schultz PG, Gray NS. A small-molecule inducer of the antioxidant response element. Chem Biol. 2010 May 28; 17(5):537-47.
View in: PubMed
Weisberg E, Deng X, Choi HG, Barrett R, Adamia S, Ray A, Moreno D, Kung AL, Gray N, Griffin JD. Beneficial effects of combining a type II ATP competitive inhibitor with an allosteric competitive inhibitor of BCR-ABL for the treatment of imatinib-sensitive and imatinib-resistant CML. Leukemia. 2010 Jul; 24(7):1375-8.
View in: PubMed
Deng X, Lim SM, Zhang J, Gray NS. Broad spectrum alkynyl inhibitors of T315I Bcr-Abl. Bioorg Med Chem Lett. 2010 Jul 15; 20(14):4196-200.
View in: PubMed
Kwiatkowski N, Jelluma N, Filippakopoulos P, Soundararajan M, Manak MS, Kwon M, Choi HG, Sim T, Deveraux QL, Rottmann S, Pellman D, Shah JV, Kops GJ, Knapp S, Gray NS. Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function. Nat Chem Biol. 2010 May; 6(5):359-68.
View in: PubMed
Zhou W, Hur W, McDermott U, Dutt A, Xian W, Ficarro SB, Zhang J, Sharma SV, Brugge J, Meyerson M, Settleman J, Gray NS. A structure-guided approach to creating covalent FGFR inhibitors. Chem Biol. 2010 Mar 26; 17(3):285-95.
View in: PubMed
Weisberg E, Choi HG, Ray A, Barrett R, Zhang J, Sim T, Zhou W, Seeliger M, Cameron M, Azam M, Fletcher JA, Debiec-Rychter M, Mayeda M, Moreno D, Kung AL, Janne PA, Khosravi-Far R, Melo JV, Manley PW, Adamia S, Wu C, Gray N, Griffin JD. Discovery of a small-molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFRalpha, Kit, and Src kinases: novel type II inhibitor of gatekeeper mutants. Blood. 2010 May 27; 115(21):4206-16.
View in: PubMed
Fabbro D, Manley PW, Jahnke W, Liebetanz J, Szyttenholm A, Fendrich G, Strauss A, Zhang J, Gray NS, Adrian F, Warmuth M, Pelle X, Grotzfeld R, Berst F, Marzinzik A, Cowan-Jacob SW, Furet P, Mestan J. Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding site. Biochim Biophys Acta. 2010 Mar; 1804(3):454-62.
View in: PubMed
McDermott U, Pusapati RV, Christensen JG, Gray NS, Settleman J. Acquired resistance of non-small cell lung cancer cells to MET kinase inhibition is mediated by a switch to epidermal growth factor receptor dependency. Cancer Res. 2010 Feb 15; 70(4):1625-34.
View in: PubMed
Zhang J, Adrián FJ, Jahnke W, Cowan-Jacob SW, Li AG, Iacob RE, Sim T, Powers J, Dierks C, Sun F, Guo GR, Ding Q, Okram B, Choi Y, Wojciechowski A, Deng X, Liu G, Fendrich G, Strauss A, Vajpai N, Grzesiek S, Tuntland T, Liu Y, Bursulaya B, Azam M, Manley PW, Engen JR, Daley GQ, Warmuth M, Gray NS. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature. 2010 Jan 28; 463(7280):501-6.
View in: PubMed
Zhou W, Ercan D, Chen L, Yun CH, Li D, Capelletti M, Cortot AB, Chirieac L, Iacob RE, Padera R, Engen JR, Wong KK, Eck MJ, Gray NS, Jänne PA. Novel mutant-selective EGFR kinase inhibitors against EGFR T790M. Nature. 2009 Dec 24; 462(7276):1070-4.
View in: PubMed
Emery CM, Vijayendran KG, Zipser MC, Sawyer AM, Niu L, Kim JJ, Hatton C, Chopra R, Oberholzer PA, Karpova MB, MacConaill LE, Zhang J, Gray NS, Sellers WR, Dummer R, Garraway LA. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci U S A. 2009 Dec 01; 106(48):20411-6.
View in: PubMed
Wu T, Nagle A, Sakata T, Henson K, Borboa R, Chen Z, Kuhen K, Plouffe D, Winzeler E, Adrian F, Tuntland T, Chang J, Simerson S, Howard S, Ek J, Isbell J, Deng X, Gray NS, Tully DC, Chatterjee AK. Cell-based optimization of novel benzamides as potential antimalarial leads. Bioorg Med Chem Lett. 2009 Dec 15; 19(24):6970-4.
View in: PubMed
Zhang G, Ren P, Gray NS, Sim T, Wang X, Liu Y, Che J, Dong W, Tian SS, Sandberg ML, Spalding TA, Romeo R, Iskandar M, Wang Z, Seidel HM, Karanewsky DS, He Y. Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors. Part II. Bioorg Med Chem Lett. 2009 Dec 01; 19(23):6691-5.
View in: PubMed
Choi Y, Seeliger MA, Panjarian SB, Kim H, Deng X, Sim T, Couch B, Koleske AJ, Smithgall TE, Gray NS. N-myristoylated c-Abl tyrosine kinase localizes to the endoplasmic reticulum upon binding to an allosteric inhibitor. J Biol Chem. 2009 Oct 16; 284(42):29005-14.
View in: PubMed
Jänne PA, Gray N, Settleman J. Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. Nat Rev Drug Discov. 2009 Sep; 8(9):709-23.
View in: PubMed
Speake G, Klinowska T, Hickinson M, Marshall G, Smith P, Vincent J, Anderton J, Gray N, Smith I, Ogilvie D. Characterization of AZD8931, a potent reversible small molecule inhibitor against epidermal growth factor receptor (EGFR), erythroblastic leukemia viral oncogene homolog 2 (HER2) and 3 (HER3) with a unique and balanced pharmacological profile. J Clin Oncol. 2009 May 20; 27(15_suppl):11072.
View in: PubMed
Weisberg E, Barrett R, Liu Q, Stone R, Gray N, Griffin JD. FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML. Drug Resist Updat. 2009 Jun; 12(3):81-9.
View in: PubMed
Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM. DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009 May 29; 137(5):873-86.
View in: PubMed
Choi Y, Syeda F, Walker JR, Finerty PJ, Cuerrier D, Wojciechowski A, Liu Q, Dhe-Paganon S, Gray NS. Discovery and structural analysis of Eph receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2009 Aug 01; 19(15):4467-70.
View in: PubMed
Goldsmith M, Avni D, Levy-Rimler G, Mashiach R, Ernst O, Levi M, Webb B, Meijler MM, Gray NS, Rosen H, Zor T. A ceramide-1-phosphate analogue, PCERA-1, simultaneously suppresses tumour necrosis factor-alpha and induces interleukin-10 production in activated macrophages. Immunology. 2009 May; 127(1):103-15.
View in: PubMed
Xian W, Pappas L, Pandya D, Selfors LM, Derksen PW, de Bruin M, Gray NS, Jonkers J, Rosen JM, Brugge JS. Fibroblast growth factor receptor 1-transformed mammary epithelial cells are dependent on RSK activity for growth and survival. Cancer Res. 2009 Mar 15; 69(6):2244-51.
View in: PubMed
Sáenz JB, Sun WJ, Chang JW, Li J, Bursulaya B, Gray NS, Haslam DB. Golgicide A reveals essential roles for GBF1 in Golgi assembly and function. Nat Chem Biol. 2009 Mar; 5(3):157-65.
View in: PubMed
Avni D, Goldsmith M, Ernst O, Mashiach R, Tuntland T, Meijler MM, Gray NS, Rosen H, Zor T. Modulation of TNFalpha, IL-10 and IL-12p40 levels by a ceramide-1-phosphate analog, PCERA-1, in vivo and ex vivo in primary macrophages. Immunol Lett. 2009 Mar 24; 123(1):1-8.
View in: PubMed
Iacob RE, Pene-Dumitrescu T, Zhang J, Gray NS, Smithgall TE, Engen JR. Conformational disturbance in Abl kinase upon mutation and deregulation. Proc Natl Acad Sci U S A. 2009 Feb 03; 106(5):1386-91.
View in: PubMed
Thoreen CC, Kang SA, Chang JW, Liu Q, Zhang J, Gao Y, Reichling LJ, Sim T, Sabatini DM, Gray NS. An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1. J Biol Chem. 2009 Mar 20; 284(12):8023-32.
View in: PubMed
Liu Q, Thoreen C, Wang J, Sabatini D, Gray NS. mTOR Mediated Anti-Cancer Drug Discovery. Drug Discov Today Ther Strateg. 2009; 6(2):47-55.
View in: PubMed
Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 2009 Jan; 9(1):28-39.
View in: PubMed
George RE, Sanda T, Hanna M, Fröhling S, Luther W, Zhang J, Ahn Y, Zhou W, London WB, McGrady P, Xue L, Zozulya S, Gregor VE, Webb TR, Gray NS, Gilliland DG, Diller L, Greulich H, Morris SW, Meyerson M, Look AT. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature. 2008 Oct 16; 455(7215):975-8.
View in: PubMed
Azam M, Seeliger MA, Gray NS, Kuriyan J, Daley GQ. Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat Struct Mol Biol. 2008 Oct; 15(10):1109-18.
View in: PubMed
Zhang G, Ren P, Gray NS, Sim T, Liu Y, Wang X, Che J, Tian SS, Sandberg ML, Spalding TA, Romeo R, Iskandar M, Chow D, Martin Seidel H, Karanewsky DS, He Y. Discovery of pyrimidine benzimidazoles as Lck inhibitors: part I. Bioorg Med Chem Lett. 2008 Oct 15; 18(20):5618-21.
View in: PubMed
Hur W, Velentza A, Kim S, Flatauer L, Jiang X, Valente D, Mason DE, Suzuki M, Larson B, Zhang J, Zagorska A, Didonato M, Nagle A, Warmuth M, Balk SP, Peters EC, Gray NS. Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase. Bioorg Med Chem Lett. 2008 Nov 15; 18(22):5916-9.
View in: PubMed
Koivunen JP, Mermel C, Zejnullahu K, Murphy C, Lifshits E, Holmes AJ, Choi HG, Kim J, Chiang D, Thomas R, Lee J, Richards WG, Sugarbaker DJ, Ducko C, Lindeman N, Marcoux JP, Engelman JA, Gray NS, Lee C, Meyerson M, Jänne PA. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer. Clin Cancer Res. 2008 Jul 01; 14(13):4275-83.
View in: PubMed
Plouffe D, Brinker A, McNamara C, Henson K, Kato N, Kuhen K, Nagle A, Adrián F, Matzen JT, Anderson P, Nam TG, Gray NS, Chatterjee A, Janes J, Yan SF, Trager R, Caldwell JS, Schultz PG, Zhou Y, Winzeler EA. In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen. Proc Natl Acad Sci U S A. 2008 Jul 01; 105(26):9059-64.
View in: PubMed
Kato N, Sakata T, Breton G, Le Roch KG, Nagle A, Andersen C, Bursulaya B, Henson K, Johnson J, Kumar KA, Marr F, Mason D, McNamara C, Plouffe D, Ramachandran V, Spooner M, Tuntland T, Zhou Y, Peters EC, Chatterjee A, Schultz PG, Ward GE, Gray N, Harper J, Winzeler EA. Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility. Nat Chem Biol. 2008 Jun; 4(6):347-56.
View in: PubMed
McDermott U, Iafrate AJ, Gray NS, Shioda T, Classon M, Maheswaran S, Zhou W, Choi HG, Smith SL, Dowell L, Ulkus LE, Kuhlmann G, Greninger P, Christensen JG, Haber DA, Settleman J. Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors. Cancer Res. 2008 May 01; 68(9):3389-95.
View in: PubMed
Goldstein DM, Gray NS, Zarrinkar PP. High-throughput kinase profiling as a platform for drug discovery. Nat Rev Drug Discov. 2008 May; 7(5):391-7.
View in: PubMed
Andersen CB, Wan Y, Chang JW, Riggs B, Lee C, Liu Y, Sessa F, Villa F, Kwiatkowski N, Suzuki M, Nallan L, Heald R, Musacchio A, Gray NS. Discovery of selective aminothiazole aurora kinase inhibitors. ACS Chem Biol. 2008 Mar 20; 3(3):180-92.
View in: PubMed
McDermott U, Sharma SV, Dowell L, Greninger P, Montagut C, Lamb J, Archibald H, Raudales R, Tam A, Lee D, Rothenberg SM, Supko JG, Sordella R, Ulkus LE, Iafrate AJ, Maheswaran S, Njauw CN, Tsao H, Drew L, Hanke JH, Ma XJ, Erlander MG, Gray NS, Haber DA, Settleman J. Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling. Proc Natl Acad Sci U S A. 2007 Dec 11; 104(50):19936-41.
View in: PubMed
Jansma A, Zhang Q, Li B, Ding Q, Uno T, Bursulaya B, Liu Y, Furet P, Gray NS, Geierstanger BH. Verification of a designed intramolecular hydrogen bond in a drug scaffold by nuclear magnetic resonance spectroscopy. J Med Chem. 2007 Nov 29; 50(24):5875-7.
View in: PubMed
Peters EC, Gray NS. Chemical proteomics identifies unanticipated targets of clinical kinase inhibitors. ACS Chem Biol. 2007 Oct 19; 2(10):661-4.
View in: PubMed
Supekova L, Supek F, Lee J, Chen S, Gray N, Pezacki JP, Schlapbach A, Schultz PG. Identification of human kinases involved in hepatitis C virus replication by small interference RNA library screening. J Biol Chem. 2008 Jan 04; 283(1):29-36.
View in: PubMed
Hong J, Lee J, Min KH, Walker JR, Peters EC, Gray NS, Cho CY, Schultz PG. Identification and characterization of small-molecule inducers of epidermal keratinocyte differentiation. ACS Chem Biol. 2007 Mar 20; 2(3):171-5.
View in: PubMed
Galkin AV, Melnick JS, Kim S, Hood TL, Li N, Li L, Xia G, Steensma R, Chopiuk G, Jiang J, Wan Y, Ding P, Liu Y, Sun F, Schultz PG, Gray NS, Warmuth M. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc Natl Acad Sci U S A. 2007 Jan 02; 104(1):270-5.
View in: PubMed
Gray NS. Drug discovery through industry-academic partnerships. Nat Chem Biol. 2006 Dec; 2(12):649-53.
View in: PubMed
Pan S, Mi Y, Pally C, Beerli C, Chen A, Guerini D, Hinterding K, Nuesslein-Hildesheim B, Tuntland T, Lefebvre S, Liu Y, Gao W, Chu A, Brinkmann V, Bruns C, Streiff M, Cannet C, Cooke N, Gray N. A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem Biol. 2006 Nov; 13(11):1227-34.
View in: PubMed
Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol. 2006 Jul; 2(7):358-64.
View in: PubMed
Okram B, Nagle A, Adrián FJ, Lee C, Ren P, Wang X, Sim T, Xie Y, Wang X, Xia G, Spraggon G, Warmuth M, Liu Y, Gray NS. A general strategy for creating “inactive-conformation” abl inhibitors. Chem Biol. 2006 Jul; 13(7):779-86.
View in: PubMed
Choi HS, Wang Z, Richmond W, He X, Yang K, Jiang T, Karanewsky D, Gu XJ, Zhou V, Liu Y, Che J, Lee CC, Caldwell J, Kanazawa T, Umemura I, Matsuura N, Ohmori O, Honda T, Gray N, He Y. Design and synthesis of 7H-pyrrolo[2,3-d]pyrimidines as focal adhesion kinase inhibitors. Part 2. Bioorg Med Chem Lett. 2006 May 15; 16(10):2689-92.
View in: PubMed
Nagle A, Hur W, Gray NS. Antimitotic agents of natural origin. Curr Drug Targets. 2006 Mar; 7(3):305-26.
View in: PubMed
Zhang Q, Liu Y, Gao F, Ding Q, Cho C, Hur W, Jin Y, Uno T, Joazeiro CA, Gray N. Discovery of EGFR selective 4,6-disubstituted pyrimidines from a combinatorial kinase-directed heterocycle library. J Am Chem Soc. 2006 Feb 22; 128(7):2182-3.
View in: PubMed
Melnick JS, Janes J, Kim S, Chang JY, Sipes DG, Gunderson D, Jarnes L, Matzen JT, Garcia ME, Hood TL, Beigi R, Xia G, Harig RA, Asatryan H, Yan SF, Zhou Y, Gu XJ, Saadat A, Zhou V, King FJ, Shaw CM, Su AI, Downs R, Gray NS, Schultz PG, Warmuth M, Caldwell JS. An efficient rapid system for profiling the cellular activities of molecular libraries. Proc Natl Acad Sci U S A. 2006 Feb 28; 103(9):3153-8.
View in: PubMed
Choi HS, Wang Z, Richmond W, He X, Yang K, Jiang T, Sim T, Karanewsky D, Gu XJ, Zhou V, Liu Y, Ohmori O, Caldwell J, Gray N, He Y. Design and synthesis of 7H-pyrrolo[2,3-d]pyrimidines as focal adhesion kinase inhibitors. Part 1. Bioorg Med Chem Lett. 2006 Apr 15; 16(8):2173-6.
View in: PubMed
Adrián FJ, Ding Q, Sim T, Velentza A, Sloan C, Liu Y, Zhang G, Hur W, Ding S, Manley P, Mestan J, Fabbro D, Gray NS. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol. 2006 Feb; 2(2):95-102.
View in: PubMed
Han S, Zhou V, Pan S, Liu Y, Hornsby M, McMullan D, Klock HE, Haugen J, Lesley SA, Gray N, Caldwell J, Gu XJ. Identification of coumarin derivatives as a novel class of allosteric MEK1 inhibitors. Bioorg Med Chem Lett. 2005 Dec 15; 15(24):5467-73.
View in: PubMed
Tang L, Li MH, Cao P, Wang F, Chang WR, Bach S, Reinhardt J, Ferandin Y, Galons H, Wan Y, Gray N, Meijer L, Jiang T, Liang DC. Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives. J Biol Chem. 2005 Sep 02; 280(35):31220-9.
View in: PubMed
Bach S, Knockaert M, Reinhardt J, Lozach O, Schmitt S, Baratte B, Koken M, Coburn SP, Tang L, Jiang T, Liang DC, Galons H, Dierick JF, Pinna LA, Meggio F, Totzke F, Schächtele C, Lerman AS, Carnero A, Wan Y, Gray N, Meijer L. Roscovitine targets, protein kinases and pyridoxal kinase. J Biol Chem. 2005 Sep 02; 280(35):31208-19.
View in: PubMed
Luesch H, Wu TY, Ren P, Gray NS, Schultz PG, Supek F. A genome-wide overexpression screen in yeast for small-molecule target identification. Chem Biol. 2005 Jan; 12(1):55-63.
View in: PubMed
Li B, Liu Y, Uno T, Gray N. Creating chemical diversity to target protein kinases. Comb Chem High Throughput Screen. 2004 Aug; 7(5):453-72.
View in: PubMed
Wu X, Ding S, Ding Q, Gray NS, Schultz PG. Small molecules that induce cardiomyogenesis in embryonic stem cells. J Am Chem Soc. 2004 Feb 18; 126(6):1590-1.
View in: PubMed
Wan Y, Hur W, Cho CY, Liu Y, Adrian FJ, Lozach O, Bach S, Mayer T, Fabbro D, Meijer L, Gray NS. Synthesis and target identification of hymenialdisine analogs. Chem Biol. 2004 Feb; 11(2):247-59.
View in: PubMed
Sanna MG, Liao J, Jo E, Alfonso C, Ahn MY, Peterson MS, Webb B, Lefebvre S, Chun J, Gray N, Rosen H. Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem. 2004 Apr 02; 279(14):13839-48.
View in: PubMed
Wignall SM, Gray NS, Chang YT, Juarez L, Jacob R, Burlingame A, Schultz PG, Heald R. Identification of a novel protein regulating microtubule stability through a chemical approach. Chem Biol. 2004 Jan; 11(1):135-46.
View in: PubMed
Ding S, Wu TY, Brinker A, Peters EC, Hur W, Gray NS, Schultz PG. Synthetic small molecules that control stem cell fate. Proc Natl Acad Sci U S A. 2003 Jun 24; 100(13):7632-7.
View in: PubMed
Chao SH, Walker JR, Chanda SK, Gray NS, Caldwell JS. Identification of homeodomain proteins, PBX1 and PREP1, involved in the transcription of murine leukemia virus. Mol Cell Biol. 2003 Feb; 23(3):831-41.
View in: PubMed
Warmuth M, Damoiseaux R, Liu Y, Fabbro D, Gray N. SRC family kinases: potential targets for the treatment of human cancer and leukemia. Curr Pharm Des. 2003; 9(25):2043-59.
View in: PubMed
Gray NS. Optimization of experimental antimitotic agents: classical and combinatorial methods. Prog Cell Cycle Res. 2003; 5:135-43.
View in: PubMed
Ruetz S, Fabbro D, Zimmermann J, Meyer T, Gray N. Chemical and biological profile of dual Cdk1 and Cdk2 inhibitors. Curr Med Chem Anticancer Agents. 2003 Jan; 3(1):1-14.
View in: PubMed
Wu X, Ding S, Ding Q, Gray NS, Schultz PG. A small molecule with osteogenesis-inducing activity in multipotent mesenchymal progenitor cells. J Am Chem Soc. 2002 Dec 11; 124(49):14520-1.
View in: PubMed
Knockaert M, Lenormand P, Gray N, Schultz P, Pouysségur J, Meijer L. p42/p44 MAPKs are intracellular targets of the CDK inhibitor purvalanol. Oncogene. 2002 Sep 19; 21(42):6413-24.
View in: PubMed
Chang YT, Choi G, Bae YS, Burdett M, Moon HS, Lee JW, Gray NS, Schultz PG, Meijer L, Chung SK, Choi KY, Suh PG, Ryu SH. Purine-based inhibitors of inositol-1,4,5-trisphosphate-3-kinase. Chembiochem. 2002 Sep 02; 3(9):897-901.
View in: PubMed
Schang LM, Bantly A, Knockaert M, Shaheen F, Meijer L, Malim MH, Gray NS, Schaffer PA. Pharmacological cyclin-dependent kinase inhibitors inhibit replication of wild-type and drug-resistant strains of herpes simplex virus and human immunodeficiency virus type 1 by targeting cellular, not viral, proteins. J Virol. 2002 Aug; 76(15):7874-82.
View in: PubMed
Ding S, Gray NS, Ding Q, Wu X, Schultz PG. Resin-capture and release strategy toward combinatorial libraries of 2,6,9-substituted purines. J Comb Chem. 2002 Mar-Apr; 4(2):183-6.
View in: PubMed
Ding S, Gray NS, Wu X, Ding Q, Schultz PG. A combinatorial scaffold approach toward kinase-directed heterocycle libraries. J Am Chem Soc. 2002 Feb 27; 124(8):1594-6.
View in: PubMed
Chang YT, Wignall SM, Rosania GR, Gray NS, Hanson SR, Su AI, Merlie J, Moon HS, Sangankar SB, Perez O, Heald R, Schultz PG. Synthesis and biological evaluation of myoseverin derivatives: microtubule assembly inhibitors. J Med Chem. 2001 Dec 20; 44(26):4497-500.
View in: PubMed
Ding S, Gray NS, Ding Q, Schultz PG. A concise and traceless linker strategy toward combinatorial libraries of 2,6,9-substituted purines. J Org Chem. 2001 Nov 30; 66(24):8273-6.
View in: PubMed
Ding S, Gray NS, Ding Q, Schultz PG. Expanding the diversity of purine libraries. Tetrahedron Lett 2001;42:8751-5
Wu TY, Ding S, Gray NS, Schultz PG. Solid-phase synthesis of 2,3,5-trisubstituted indoles. Org Lett. 2001 Nov 29; 3(24):3827-30.
View in: PubMed
Lin Q, Jiang F, Schultz PG, Gray NS. Design of allele-specific protein methyltransferase inhibitors. J Am Chem Soc. 2001 Nov 28; 123(47):11608-13.
View in: PubMed
Gray NS. Combinatorial libraries and biological discovery. Curr Opin Neurobiol. 2001 Oct; 11(5):608-14.
View in: PubMed
Verdugo DE, Cancilla MT, Ge X, Gray NS, Chang YT, Schultz PG, Negishi M, Leary JA, Bertozzi CR. Discovery of estrogen sulfotransferase inhibitors from a purine library screen. J Med Chem. 2001 Aug 16; 44(17):2683-6.
View in: PubMed
Harmse L, van Zyl R, Gray N, Schultz P, Leclerc S, Meijer L, Doerig C, Havlik I. Structure-activity relationships and inhibitory effects of various purine derivatives on the in vitro growth of Plasmodium falciparum. Biochem Pharmacol. 2001 Aug 01; 62(3):341-8.
View in: PubMed
Bishop AC, Ubersax JA, Petsch DT, Matheos DP, Gray NS, Blethrow J, Shimizu E, Tsien JZ, Schultz PG, Rose MD, Wood JL, Morgan DO, Shokat KM. A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature. 2000 Sep 21; 407(6802):395-401.
View in: PubMed
Armstrong JI, Portley AR, Chang YT, Nierengarten DM, Cook BN, Bowman KG, Bishop A, Gray NS, Shokat KM, Schultz PG, Bertozzi CR. Discovery of Carbohydrate Sulfotransferase Inhibitors from a Kinase-Directed Library. Angew Chem Int Ed Engl 2000;39:1303-6.
Knockaert M, Gray N, Damiens E, Chang YT, Grellier P, Grant K, Fergusson D, Mottram J, Soete M, Dubremetz JF, Le Roch K, Doerig C, Schultz P, Meijer L. Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors. Chem Biol. 2000 Jun; 7(6):411-22.
View in: PubMed
Gray N, Détivaud L, Doerig C, Meijer L. ATP-site directed inhibitors of cyclin-dependent kinases. Curr Med Chem. 1999 Sep; 6(9):859-75.
View in: PubMed
Chang YT, Gray NS, Rosania GR, Sutherlin DP, Kwon S, Norman TC, Sarohia R, Leost M, Meijer L, Schultz PG. Synthesis and application of functionally diverse 2,6,9-trisubstituted purine libraries as CDK inhibitors. Chem Biol. 1999 Jun; 6(6):361-75.
View in: PubMed
Rosania GR, Merlie J, Gray N, Chang YT, Schultz PG, Heald R. A cyclin-dependent kinase inhibitor inducing cancer cell differentiation: biochemical identification using Xenopus egg extracts. Proc Natl Acad Sci U S A. 1999 Apr 27; 96(9):4797-802.
View in: PubMed
Gray NS, Wodicka L, Thunnissen AM, Norman TC, Kwon S, Espinoza FH, Morgan DO, Barnes G, LeClerc S, Meijer L, Kim SH, Lockhart DJ, Schultz PG. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors. Science. 1998 Jul 24; 281(5376):533-8.
View in: PubMed
Brooks EE, Gray NS, Joly A, Kerwar SS, Lum R, Mackman RL, Norman TC, Rosete J, Rowe M, Schow SR, Schultz PG, Wang X, Wick MM, Shiffman D. CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation. J Biol Chem. 1997 Nov 14; 272(46):29207-11.
View in: PubMed
Gray NS, Kwon S, Schultz PG. Combinatorial synthesis of 2,9-substituted purines. Tetrahedron Lett. 1997; 38:1161-4.
Norman TC, Gray NS, Koh JT, Schultz PG. A structure-based approach to kinase inhibitors. J Am Chem Soc 1996;118:7430-1.
Patten PA, Gray NS, Yang PL, Marks CB, Wedemayer GJ, Boniface JJ, Stevens RC, Schultz PG. The immunological evolution of catalysis. Science. 1996 Feb 23; 271(5252):1086-91.
View in: PubMed
