1235034-86-2Relevant academic research and scientific papers
Discovery of a potent and selective BCL-XLinhibitor with in vivo activity
Tao, Zhi-Fu,Hasvold, Lisa,Wang, Le,Wang, Xilu,Petros, Andrew M.,Park, Chang H.,Boghaert, Erwin R.,Catron, Nathaniel D.,Chen, Jun,Colman, Peter M.,Czabotar, Peter E.,Deshayes, Kurt,Fairbrother, Wayne J.,Flygare, John A.,Hymowitz, Sarah G.,Jin, Sha,Judge, Russell A.,Koehler, Michael F. T.,Kovar, Peter J.,Lessene, Guillaume,Mitten, Michael J.,Ndubaku, Chudi O.,Nimmer, Paul,Purkey, Hans E.,Oleksijew, Anatol,Phillips, Darren C.,Sleebs, Brad E.,Smith, Brian J.,Smith, Morey L.,Tahir, Stephen K.,Watson, Keith G.,Xiao, Yu,Xue, John,Zhang, Haichao,Zobel, Kerry,Rosenberg, Saul H.,Tse, Chris,Leverson, Joel D.,Elmore, Steven W.,Souers, Andrew J.
, p. 1088 - 1093 (2014)
A-1155463, a highly potent and selective BCL-XLinhibitor, was discovered through nuclear magnetic resonance (NMR) fragment screening and structure-based design. This compound is substantially more potent against BCL-XL-dependent cell lines relative to our recently reported inhibitor, WEHI-539, while possessing none of its inherent pharmaceutical liabilities. A-1155463 caused a mechanism-based and reversible thrombocytopenia in mice and inhibited H146 small cell lung cancer xenograft tumor growth in vivo following multiple doses. A-1155463 thus represents an excellent tool molecule for studying BCL-XLbiology as well as a productive lead structure for further optimization.
HETEROCYCLIC COMPOUNDS AND METHODS OF USE
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Page/Page column 108, (2010/08/04)
In one aspect, the present invention provides for a compound of Formula I; in which the variable X1a, X1b, X1c, X1d, Q, A, R1, B, L, E, and the subscripts m and n have the meanings as described herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-xL proteins.
