Discovery of a potent and selective BCL-XL inhibitor with in vivo activity
Details
Publication Year 2014-08-26, Volume 5, Issue #10, Page 1088-93
Journal Title
ACS Med Chem Lett
Publication Type
Journal Article
Abstract
A-1155463, a highly potent and selective BCL-XL inhibitor, 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-XL biology as well as a productive lead structure for further optimization.
Publisher
ACS
WEHI Research Division(s)
Structural Biology; Chemical Biology
Publisher's Version
https://doi.org/10.1021/ml5001867
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2014-10-16 03:19:24
Last Modified: 2015-03-24 09:55:31
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