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

J Med Chem. 2004 Aug 12;47(17):4163-5. doi: 10.1021/jm034182u.

Abstract

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.

MeSH terms

  • Cell Line, Tumor
  • Databases, Factual
  • Genes, Reporter
  • Humans
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / metabolism*
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2
  • Quantitative Structure-Activity Relationship
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Sulfonamides
  • Tumor Suppressor Protein p53
  • Luciferases
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2