Document Report Card

ID: ALA1240488

Journal: J Med Chem

Title: Nonpeptidic and potent small-molecule inhibitors of cIAP-1/2 and XIAP proteins.

Authors: Sun H, Lu J, Liu L, Yi H, Qiu S, Yang CY, Deschamps JR, Wang S.

Abstract: A series of compounds were designed and synthesized as antagonists of cIAP-1/2 and XIAP based upon our previously identified lead compound SM-122 (1). The most potent of these (7) binds to XIAP, cIAP-1, and cIAP-2 proteins with K(i) values of 36, <1, and <1.9 nM, respectively. Consistent with its potent binding affinities to IAPs, 7 effectively antagonizes XIAP in a cell-free caspase-9 functional assay, efficiently induces cIAP-1 degradation in cells at concentrations as low as 10 nM, and triggers activation of caspases and PARP cleavage in the MDA-MB-231 breast cancer cell line. Compound 7 potently inhibits cell growth in the MDA-MB-231 cancer cell line with an IC(50) value of 200 nM and is 9 times more potent than compound 1.

CiteXplore: 20684551

DOI: 10.1021/jm100487z