Design, Synthesis, and Evaluation of Potent, Nonpeptidic Mimetics of Second Mitochondria-Derived Activator of Caspases
A series of new Smac mimetics have been designed, synthesized, and evaluated. The most potent compound 10 binds to XIAP, cIAP-1, and cIAP-2 BIR3 proteins with K i of 3.9, 0.37, and 0.25 nM, respectively. Compound 10 antagonizes XIAP in a cell-free functional assay and induces rapid cIAP-1 degradatio...
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Published in | Journal of medicinal chemistry Vol. 52; no. 3; pp. 593 - 596 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
12.02.2009
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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Summary: | A series of new Smac mimetics have been designed, synthesized, and evaluated. The most potent compound 10 binds to XIAP, cIAP-1, and cIAP-2 BIR3 proteins with K i of 3.9, 0.37, and 0.25 nM, respectively. Compound 10 antagonizes XIAP in a cell-free functional assay and induces rapid cIAP-1 degradation in cancer cells. Compound 10 inhibits cell growth in the MDA-MB-231 cancer cell line with an IC50 of 8.9 nM. |
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Bibliography: | NIH RePORTER ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/jm801101z |