| Literature DB >> 22608393 |
Gretchen M Schroeder1, Donna Wei, Patrizia Banfi, Zhen-Wei Cai, Jonathan Lippy, Maria Menichincheri, Michele Modugno, Joseph Naglich, Becky Penhallow, Heidi L Perez, John Sack, Robert J Schmidt, Andrew Tebben, Chunhong Yan, Liping Zhang, Arturo Galvani, Louis J Lombardo, Robert M Borzilleri.
Abstract
5-Butyl-1,4-diphenyl pyrazole and 2-amino-5-chloro pyrimidine acylsulfonamides were developed as potent dual antagonists of Bcl-2 and Bcl-xL. Compounds were optimized for binding to the I88, L92, I95, and F99 pockets normally occupied by pro-apoptotic protein Bim. An X-ray crystal structure confirmed the proposed binding mode. Observation of cytochrome c release from isolated mitochondria in MV-411 cells provides further evidence of target inhibition. Compounds demonstrated submicromolar antiproliferative activity in Bcl-2/Bcl-xL dependent cell lines.Entities:
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Year: 2012 PMID： 22608393 DOI： 10.1016/j.bmcl.2012.04.106
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823