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Publication Abstract from PubMed

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.

Pyrazole and pyrimidine phenylacylsulfonamides as dual Bcl-2/Bcl-xL antagonists.,Schroeder GM, Wei D, Banfi P, Cai ZW, Lippy J, Menichincheri M, Modugno M, Naglich J, Penhallow B, Perez HL, Sack J, Schmidt RJ, Tebben A, Yan C, Zhang L, Galvani A, Lombardo LJ, Borzilleri RM Bioorg Med Chem Lett. 2012 Jun 15;22(12):3951-6. Epub 2012 Apr 30. PMID:22608393^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.