A nonpeptidic sulfonamide inhibits the p53-mdm2 interaction and activates p53-dependent transcription in mdm2-overexpressing cells

The evaluation of a sulfonamide inhibitor of the p53-mdm2 interaction is presented. The compound was identified using 3D database searching techniques based on a computationally derived pharmacophore model of mdm2 binding. It inhibits the physical interaction of recombinant p53 and mdm2 in vitro and increases p53-dependent transcription in an mdm2-overexpressing cell line.