Document Report Card

ID: ALA1140231

Journal: J Med Chem

Title: Design, synthesis, and evaluation of tricyclic, conformationally constrained small-molecule mimetics of second mitochondria-derived activator of caspases.

Authors: Zhang B, Nikolovska-Coleska Z, Zhang Y, Bai L, Qiu S, Yang CY, Sun H, Wang S, Wu Y.

Abstract: A series of tricyclic, conformationally constrained Smac mimetics have been designed, synthesized, and evaluated. The most potent compound 6 (WS-5) binds to XIAP, cIAP-1, and cIAP-2 with K(i) of 18, 1.1, and 4.2 nM, respectively. Compound 6 antagonizes XIAP in a functional assay, induces cIAP-1 degradation, inhibits cell growth with an IC(50) of 68 nM in the MDA-MB-231 cancer cell line, and effectively induces cancer cells to undergo apoptosis.

CiteXplore: 19012392

DOI: 10.1021/jm801146d