Structure-Based Design of Spiro-oxindoles as Potent, Specific Small-Molecule Inhibitors of the MDM2−p53 Interaction
National Institutes of Health · National Cancer Institute · +1 more institution
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.
Citation impact
- FWCI
- 11.07
- Percentile
- 100%
- References
- 20
Authors
12- KDKe DingCorresponding
National Institutes of Health, National Cancer Institute, University of Michigan–Ann Arbor
- YLYipin Lu
National Cancer Institute, University of Michigan–Ann Arbor, National Institutes of Health
- ZNZaneta Nikolovska‐Coleska
University of Michigan–Ann Arbor, National Cancer Institute, National Institutes of Health
- GWGuoping Wang
University of Michigan–Ann Arbor, National Cancer Institute, National Institutes of Health
- SQSu Qiu
National Institutes of Health, National Cancer Institute, University of Michigan–Ann Arbor
Topics & keywords
- Chemistry
- Structure–activity relationship
- Small molecule
- Molecule
- Stereochemistry
- Mdm2
- Combinatorial chemistry
- Computational biology
- Good health and well-being