Abstract
Potent and selective small-molecule inhibitors of the p53-MDM2 interaction intended for the treatment of p53 wild-type tumors have been designed and optimized in a number of chemical series. This review details recent disclosures of compounds in advanced optimization and features key series that have given rise to clinical trial candidates. The structure–activity relationships for inhibitor classes are discussed with reference to x-ray structures, and common structural features are identified.
Financial & competing interests disclosure
The authors thank Cancer Research UK and Newcastle University for financial support. B Zhang, BT Golding and IR Hardcastle are part of a collaborative research project between Newcastle University and Astex Pharmaceuticals Ltd towards small-molecule MDM2-p53 inhibitors. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.