Potent and Orally Active Small-Molecule Inhibitors of the MDM2−p53 Interaction
Journal of Medicinal Chemistry2009Vol. 52(24), pp. 7970–7973
Citations Over TimeTop 10% of 2009 papers
Shanghai Yu, Dongguang Qin, Sanjeev Shangary, Jianyong Chen, Guoping Wang, Ke Ding, Donna McEachern, Su Qiu, Zaneta Nikolovska‐Coleska, Rebecca S. Miller, Sunghyun Kang, Dajun Yang, Shaomeng Wang
Abstract
We report herein the design of potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. Compound 5 binds to MDM2 with a K(i) of 0.6 nM, activates p53 at concentrations as low as 40 nM, and potently and selectively inhibits cell growth in tumor cells with wild-type p53 over tumor cells with mutated/deleted p53. Compound 5 has a good oral bioavailability and effectively inhibits tumor growth in the SJSA-1 xenograft model.
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