| Literature DB >> 23651223 |
Rong Sheng1, Haiying Sun, Liu Liu, Jianfeng Lu, Donna McEachern, Guanfeng Wang, Jianfeng Wen, Ping Min, Zhenyun Du, Huirong Lu, Sanmao Kang, Ming Guo, Dajun Yang, Shaomeng Wang.
Abstract
We have designed, synthesized, and evaluated a series of new compounds based upon our previously reported bivalent Smac mimetics. This led to the identification of compound 12 (SM-1200), which binds to XIAP, cIAP1, and cIAP2 with Ki values of 0.5, 3.7, and 5.4 nM, respectively, inhibits cell growth in the MDA-MB-231 breast cancer and SK-OV-3 ovarian cancer cell lines with IC50 values of 11.0 and 28.2 nM, respectively. Compound 12 has a much improved pharmacokinetic profile over our previously reported bivalent Smac mimetics and is highly effective in induction of rapid and durable tumor regression in the MDA-MB-231 xenograft model. These data indicate that compound 12 is a promising Smac mimetic and warrants extensive evaluation as a potential candidate for clinical development.Entities:
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Year: 2013 PMID： 23651223 PMCID： PMC3806058 DOI： 10.1021/jm400216d
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446