Structure-Based Design of Spiro-oxindoles as Potent, Specific Small-Molecule Inhibitors of the MDM2−p53 Interaction
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- 13 May 2006
- journal article
- letter
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 49 (12), 3432-3435
- https://doi.org/10.1021/jm051122a
Abstract
Potent, specific, non-peptide small-molecule inhibitors of the MDM2−p53 interaction were successfully designed. The most potent inhibitor (MI-63) has a Ki value of 3 nM binding to MDM2 and greater than 10 000-fold selectivity over Bcl-2/Bcl-xL proteins. MI-63 is highly effective in activation of p53 function and in inhibition of cell growth in cancer cells with wild-type p53 status. MI-63 has excellent specificity over cancer cells with deleted p53 and shows a minimal toxicity to normal cells.Keywords
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