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Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases.
Chen YN, LaMarche MJ, Chan HM, Fekkes P, Garcia-Fortanet J, Acker MG, Antonakos B, Chen CH, Chen Z, Cooke VG, Dobson JR, Deng Z, Fei F, Firestone B, Fodor M, Fridrich C, Gao H, Grunenfelder D, Hao HX, Jacob J, Ho S, Hsiao K, Kang ZB, Karki R, Kato M, Larrow J, La Bonte LR, Lenoir F, Liu G, Liu S, Majumdar D, Meyer MJ, Palermo M, Perez L, Pu M, Price E, Quinn C, Shakya S, Shultz MD, Slisz J, Venkatesan K, Wang P, Warmuth M, Williams S, Yang G, Yuan J, Zhang JH, Zhu P, Ramsey T, Keen NJ, Sellers WR, Stams T, Fortin PD. Chen YN, et al. Among authors: keen nj. Nature. 2016 Jul 7;535(7610):148-52. doi: 10.1038/nature18621. Epub 2016 Jun 29. Nature. 2016. PMID: 27362227
Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor.
Garcia Fortanet J, Chen CH, Chen YN, Chen Z, Deng Z, Firestone B, Fekkes P, Fodor M, Fortin PD, Fridrich C, Grunenfelder D, Ho S, Kang ZB, Karki R, Kato M, Keen N, LaBonte LR, Larrow J, Lenoir F, Liu G, Liu S, Lombardo F, Majumdar D, Meyer MJ, Palermo M, Perez L, Pu M, Ramsey T, Sellers WR, Shultz MD, Stams T, Towler C, Wang P, Williams SL, Zhang JH, LaMarche MJ. Garcia Fortanet J, et al. J Med Chem. 2016 Sep 8;59(17):7773-82. doi: 10.1021/acs.jmedchem.6b00680. Epub 2016 Jul 12. J Med Chem. 2016. PMID: 27347692
Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer.
LaMarche MJ, Acker M, Argintaru A, Bauer D, Boisclair J, Chan H, Chen CH, Chen YN, Chen Z, Deng Z, Dore M, Dunstan D, Fan J, Fekkes P, Firestone B, Fodor M, Garcia-Fortanet J, Fortin PD, Fridrich C, Giraldes J, Glick M, Grunenfelder D, Hao HX, Hentemann M, Ho S, Jouk A, Kang ZB, Karki R, Kato M, Keen N, Koenig R, LaBonte LR, Larrow J, Liu G, Liu S, Majumdar D, Mathieu S, Meyer MJ, Mohseni M, Ntaganda R, Palermo M, Perez L, Pu M, Ramsey T, Reilly J, Sarver P, Sellers WR, Sendzik M, Shultz MD, Slisz J, Slocum K, Smith T, Spence S, Stams T, Straub C, Tamez V Jr, Toure BB, Towler C, Wang P, Wang H, Williams SL, Yang F, Yu B, Zhang JH, Zhu S. LaMarche MJ, et al. J Med Chem. 2020 Nov 25;63(22):13578-13594. doi: 10.1021/acs.jmedchem.0c01170. Epub 2020 Sep 24. J Med Chem. 2020. PMID: 32910655
The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1.
Wylie AA, Schoepfer J, Jahnke W, Cowan-Jacob SW, Loo A, Furet P, Marzinzik AL, Pelle X, Donovan J, Zhu W, Buonamici S, Hassan AQ, Lombardo F, Iyer V, Palmer M, Berellini G, Dodd S, Thohan S, Bitter H, Branford S, Ross DM, Hughes TP, Petruzzelli L, Vanasse KG, Warmuth M, Hofmann F, Keen NJ, Sellers WR. Wylie AA, et al. Among authors: keen nj. Nature. 2017 Mar 30;543(7647):733-737. doi: 10.1038/nature21702. Epub 2017 Mar 22. Nature. 2017. PMID: 28329763
Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia.
Jaffe JD, Wang Y, Chan HM, Zhang J, Huether R, Kryukov GV, Bhang HE, Taylor JE, Hu M, Englund NP, Yan F, Wang Z, Robert McDonald E 3rd, Wei L, Ma J, Easton J, Yu Z, deBeaumount R, Gibaja V, Venkatesan K, Schlegel R, Sellers WR, Keen N, Liu J, Caponigro G, Barretina J, Cooke VG, Mullighan C, Carr SA, Downing JR, Garraway LA, Stegmeier F. Jaffe JD, et al. Nat Genet. 2013 Nov;45(11):1386-91. doi: 10.1038/ng.2777. Epub 2013 Sep 29. Nat Genet. 2013. PMID: 24076604 Free PMC article.
High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.
Gao H, Korn JM, Ferretti S, Monahan JE, Wang Y, Singh M, Zhang C, Schnell C, Yang G, Zhang Y, Balbin OA, Barbe S, Cai H, Casey F, Chatterjee S, Chiang DY, Chuai S, Cogan SM, Collins SD, Dammassa E, Ebel N, Embry M, Green J, Kauffmann A, Kowal C, Leary RJ, Lehar J, Liang Y, Loo A, Lorenzana E, Robert McDonald E 3rd, McLaughlin ME, Merkin J, Meyer R, Naylor TL, Patawaran M, Reddy A, Röelli C, Ruddy DA, Salangsang F, Santacroce F, Singh AP, Tang Y, Tinetto W, Tobler S, Velazquez R, Venkatesan K, Von Arx F, Wang HQ, Wang Z, Wiesmann M, Wyss D, Xu F, Bitter H, Atadja P, Lees E, Hofmann F, Li E, Keen N, Cozens R, Jensen MR, Pryer NK, Williams JA, Sellers WR. Gao H, et al. Nat Med. 2015 Nov;21(11):1318-25. doi: 10.1038/nm.3954. Epub 2015 Oct 19. Nat Med. 2015. PMID: 26479923
Studying clonal dynamics in response to cancer therapy using high-complexity barcoding.
Bhang HE, Ruddy DA, Krishnamurthy Radhakrishna V, Caushi JX, Zhao R, Hims MM, Singh AP, Kao I, Rakiec D, Shaw P, Balak M, Raza A, Ackley E, Keen N, Schlabach MR, Palmer M, Leary RJ, Chiang DY, Sellers WR, Michor F, Cooke VG, Korn JM, Stegmeier F. Bhang HE, et al. Nat Med. 2015 May;21(5):440-8. doi: 10.1038/nm.3841. Epub 2015 Apr 13. Nat Med. 2015. PMID: 25849130
ERG signaling in prostate cancer is driven through PRMT5-dependent methylation of the Androgen Receptor.
Mounir Z, Korn JM, Westerling T, Lin F, Kirby CA, Schirle M, McAllister G, Hoffman G, Ramadan N, Hartung A, Feng Y, Kipp DR, Quinn C, Fodor M, Baird J, Schoumacher M, Meyer R, Deeds J, Buchwalter G, Stams T, Keen N, Sellers WR, Brown M, Pagliarini RA. Mounir Z, et al. Elife. 2016 May 16;5:e13964. doi: 10.7554/eLife.13964. Elife. 2016. PMID: 27183006 Free PMC article.
Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF.
Shao W, Mishina YM, Feng Y, Caponigro G, Cooke VG, Rivera S, Wang Y, Shen F, Korn JM, Mathews Griner LA, Nishiguchi G, Rico A, Tellew J, Haling JR, Aversa R, Polyakov V, Zang R, Hekmat-Nejad M, Amiri P, Singh M, Keen N, Dillon MP, Lees E, Ramurthy S, Sellers WR, Stuart DD. Shao W, et al. Cancer Res. 2018 Mar 15;78(6):1537-1548. doi: 10.1158/0008-5472.CAN-17-2033. Epub 2018 Jan 17. Cancer Res. 2018. PMID: 29343524
Disordered methionine metabolism in MTAP/CDKN2A-deleted cancers leads to dependence on PRMT5.
Mavrakis KJ, McDonald ER 3rd, Schlabach MR, Billy E, Hoffman GR, deWeck A, Ruddy DA, Venkatesan K, Yu J, McAllister G, Stump M, deBeaumont R, Ho S, Yue Y, Liu Y, Yan-Neale Y, Yang G, Lin F, Yin H, Gao H, Kipp DR, Zhao S, McNamara JT, Sprague ER, Zheng B, Lin Y, Cho YS, Gu J, Crawford K, Ciccone D, Vitari AC, Lai A, Capka V, Hurov K, Porter JA, Tallarico J, Mickanin C, Lees E, Pagliarini R, Keen N, Schmelzle T, Hofmann F, Stegmeier F, Sellers WR. Mavrakis KJ, et al. Science. 2016 Mar 11;351(6278):1208-13. doi: 10.1126/science.aad5944. Epub 2016 Feb 11. Science. 2016. PMID: 26912361
40 results