Structure-Based Design of Spiro-oxindoles as Potent, Specific Small-Molecule Inhibitors of the MDM2−p53 Interaction
Journal of Medicinal Chemistry2006Vol. 49(12), pp. 3432–3435
Citations Over TimeTop 10% of 2006 papers
Ke Ding, Yipin Lu, Zaneta Nikolovska‐Coleska, Guoping Wang, Su Qiu, Sanjeev Shangary, Wei Gao, Dongguang Qin, Jeanne A. Stuckey, Krzysztof Krajewski, Peter P. Roller, Shaomeng Wang
Abstract
Potent, specific, non-peptide small-molecule inhibitors of the MDM2-p53 interaction were successfully designed. The most potent inhibitor (MI-63) has a K(i) 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.
Related Papers
- → Mechanism-specific signatures for small-molecule p53 activators(2011)53 cited
- → Anticancer strategies by upregulating p53 through inhibition of its ubiquitination by MDM2(2020)26 cited
- The regulation of MDM2 oncogene and its impact on human cancers(2014)
- → Oncogenic c-Myc-induced lymphomagenesis is inhibited non-redundantly by the p19Arf–Mdm2–p53 and RP–Mdm2–p53 pathways(2020)1 cited
- → Tumor suppression and normal aging in mice with constitutively high p53 activity(2006)212 cited