Design of libraries targeting protein-protein interfaces

ChemMedChem. 2013 May;8(5):726-32. doi: 10.1002/cmdc.201200540. Epub 2013 Feb 21.

Abstract

TARGETING PPIS: A novel strategy for designing libraries targeting protein-protein interfaces enabled us to identify diverse chemical entry points to interact with therapeutic targets for which conventional screening libraries delivered no or only few hit structures. The concept was experimentally validated by early hit evaluation in biochemical screens and early ADMET profiling.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Protein Binding / drug effects
  • Protein Interaction Domains and Motifs / drug effects*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-mdm2 / chemistry
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Rats
  • Reference Standards
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Solubility
  • Structure-Activity Relationship
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Small Molecule Libraries
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2