| Literature DB >> 21443232 |
Qian Cai1, Haiying Sun, Yuefeng Peng, Jianfeng Lu, Zaneta Nikolovska-Coleska, Donna McEachern, Liu Liu, Su Qiu, Chao-Yie Yang, Rebecca Miller, Han Yi, Tao Zhang, Duxin Sun, Sanmao Kang, Ming Guo, Lance Leopold, Dajun Yang, Shaomeng Wang.
Abstract
We report the discovery and characterization of SM-406 (compound 2), a potent and orally bioavailable Smac mimetic and an antagonist of the inhibitor of apoptosis proteins (IAPs). This compound binds to XIAP, cIAP1, and cIAP2 proteins with K(i) of 66.4, 1.9, and 5.1 nM, respectively. Compound 2 effectively antagonizes XIAP BIR3 protein in a cell-free functional assay, induces rapid degradation of cellular cIAP1 protein, and inhibits cancer cell growth in various human cancer cell lines. It has good oral bioavailability in mice, rats, non-human primates, and dogs, is highly effective in induction of apoptosis in xenograft tumors, and is capable of complete inhibition of tumor growth. Compound 2 is currently in phase I clinical trials for the treatment of human cancer.Entities:
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Year: 2011 PMID： 21443232 PMCID： PMC3520070 DOI： 10.1021/jm101505d
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446