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AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance.
O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, Adrian LT, Zhou T, Huang WS, Xu Q, Metcalf CA 3rd, Tyner JW, Loriaux MM, Corbin AS, Wardwell S, Ning Y, Keats JA, Wang Y, Sundaramoorthi R, Thomas M, Zhou D, Snodgrass J, Commodore L, Sawyer TK, Dalgarno DC, Deininger MW, Druker BJ, Clackson T. O'Hare T, et al. Among authors: xu q. Cancer Cell. 2009 Nov 6;16(5):401-12. doi: 10.1016/j.ccr.2009.09.028. Cancer Cell. 2009. PMID: 19878872 Free PMC article.
Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant.
Huang WS, Metcalf CA, Sundaramoorthi R, Wang Y, Zou D, Thomas RM, Zhu X, Cai L, Wen D, Liu S, Romero J, Qi J, Chen I, Banda G, Lentini SP, Das S, Xu Q, Keats J, Wang F, Wardwell S, Ning Y, Snodgrass JT, Broudy MI, Russian K, Zhou T, Commodore L, Narasimhan NI, Mohemmad QK, Iuliucci J, Rivera VM, Dalgarno DC, Sawyer TK, Clackson T, Shakespeare WC. Huang WS, et al. Among authors: xu q. J Med Chem. 2010 Jun 24;53(12):4701-19. doi: 10.1021/jm100395q. J Med Chem. 2010. PMID: 20513156
Crystal structure of the T315I mutant of AbI kinase.
Zhou T, Parillon L, Li F, Wang Y, Keats J, Lamore S, Xu Q, Shakespeare W, Dalgarno D, Zhu X. Zhou T, et al. Among authors: xu q. Chem Biol Drug Des. 2007 Sep;70(3):171-81. doi: 10.1111/j.1747-0285.2007.00556.x. Chem Biol Drug Des. 2007. PMID: 17718712
Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant.
Thomas M, Huang WS, Wen D, Zhu X, Wang Y, Metcalf CA, Liu S, Chen I, Romero J, Zou D, Sundaramoorthi R, Li F, Qi J, Cai L, Zhou T, Commodore L, Xu Q, Keats J, Wang F, Wardwell S, Ning Y, Snodgrass JT, Broudy MI, Russian K, Iuliucci J, Rivera VM, Sawyer TK, Dalgarno DC, Clackson T, Shakespeare WC. Thomas M, et al. Among authors: xu q. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8. doi: 10.1016/j.bmcl.2011.04.060. Epub 2011 Apr 22. Bioorg Med Chem Lett. 2011. PMID: 21561767
Novel N9-arenethenyl purines as potent dual Src/Abl tyrosine kinase inhibitors.
Wang Y, Shakespeare WC, Huang WS, Sundaramoorthi R, Lentini S, Das S, Liu S, Banda G, Wen D, Zhu X, Xu Q, Keats J, Wang F, Wardwell S, Ning Y, Snodgrass JT, Broudy MI, Russian K, Dalgarno D, Clackson T, Sawyer TK. Wang Y, et al. Among authors: xu q. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4907-12. doi: 10.1016/j.bmcl.2008.06.042. Epub 2008 Jun 18. Bioorg Med Chem Lett. 2008. PMID: 18691885
9-(Arenethenyl)purines as dual Src/Abl kinase inhibitors targeting the inactive conformation: design, synthesis, and biological evaluation.
Huang WS, Zhu X, Wang Y, Azam M, Wen D, Sundaramoorthi R, Thomas RM, Liu S, Banda G, Lentini SP, Das S, Xu Q, Keats J, Wang F, Wardwell S, Ning Y, Snodgrass JT, Broudy MI, Russian K, Daley GQ, Iuliucci J, Dalgarno DC, Clackson T, Sawyer TK, Shakespeare WC. Huang WS, et al. Among authors: xu q. J Med Chem. 2009 Aug 13;52(15):4743-56. doi: 10.1021/jm900166t. J Med Chem. 2009. PMID: 19572547
Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase.
Huang WS, Liu S, Zou D, Thomas M, Wang Y, Zhou T, Romero J, Kohlmann A, Li F, Qi J, Cai L, Dwight TA, Xu Y, Xu R, Dodd R, Toms A, Parillon L, Lu X, Anjum R, Zhang S, Wang F, Keats J, Wardwell SD, Ning Y, Xu Q, Moran LE, Mohemmad QK, Jang HG, Clackson T, Narasimhan NI, Rivera VM, Zhu X, Dalgarno D, Shakespeare WC. Huang WS, et al. Among authors: xu q, xu r, xu y. J Med Chem. 2016 May 26;59(10):4948-64. doi: 10.1021/acs.jmedchem.6b00306. Epub 2016 May 12. J Med Chem. 2016. PMID: 27144831
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