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Synfacts 2006(2): 0108-0108  
DOI: 10.1055/s-2005-923597
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Spiro-oxindole MDM2 Inhibitors

Contributor(s): Philip Kocienski, Fiona Black
K. Ding, Y. Lu, Z. Nikolovska-Coleska, S. Qiu, Y. Ding, W. Gao, J. Stuckey, K. Krajewski, P. P. Roller, Y. Tomita, D. A. Parrish, J. R. Deschamps, S. Wang*
University of Michigan, National Cancer Institute-Frederick, Georgetown University Medical Center (Washington) and Naval Research Laboratory Center (Washington), USA
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Publication History

Publication Date:
23 January 2006 (online)

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Significance

The protein p53 controls cell apoptosis and acts as a tumor suppressor. It is therefore an attractive target for cancer treatment. MDM2 is an endogenous inhibitor of p53 and inhibitors of the MDM2-p53 interaction could be effective anti-cancer drugs. A structure-based design strategy was employed in the search for novel, non-peptide, and small-molecule MDM2 inhibitors. Spiro-oxindole A has an IC50 value of 0.83 µM against p53 wild-type LNCaP human prostate cancer cells.