rg7388 and 2-oxindole

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.

Topics: Animals; Antineoplastic Agents; Clinical Trials as Topic; Crystallography, X-Ray; Humans; Imidazoles; Indoles; Models, Molecular; Neoplasms; Oxindoles; para-Aminobenzoates; Piperazines; Protein Interaction Maps; Proto-Oncogene Proteins c-mdm2; Pyrrolidines; Small Molecule Libraries; Structure-Activity Relationship; Tumor Suppressor Protein p53