【文章名】Design, Synthesis, and Evaluation of Tricyclic, Conformationally Constrained Small-Molecule Mimetics of Second Mitochondria-Derived Activator of Caspases.
Design, Synthesis, and Evaluation of Tricyclic, Conformationally Constrained Small-Molecule Mimetics of Second Mitochondria-Derived Activator of Caspases.
[摘要]：A series of tricyclic, conformationally constrained Smac mimetics have been designed, synthesized, and evaluated. The most potent compd. 6 (WS-5) binds to XIAP, cIAP-1, and cIAP-2 with Ki of 18, 1.1, and 4.2 nM, resp. Compd. 6 antagonizes XIAP in a functional assay, induces cIAP-1 degrdn., inhibits cell growth with an IC50 of 68 nM in the MDA-MB-231 cancer cell line, and effectively induces cancer cells to undergo apoptosis.
