Virtual screening and experimental validation reveal novel small-molecule inhibitors of 14-3-3 protein-protein interactions

Chem Commun (Camb). 2013 Oct 4;49(76):8468-70. doi: 10.1039/c3cc44612c.

Abstract

We report first non-covalent and exclusively extracellular inhibitors of 14-3-3 protein-protein interactions identified by virtual screening. Optimization by crystal structure analysis and in vitro binding assays yielded compounds capable of disrupting the interaction of 14-3-3σ with aminopeptidase N in a cellular assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Fibroblasts / chemistry
  • Fibroblasts / cytology
  • High-Throughput Screening Assays*
  • Humans
  • Lung / chemistry
  • Lung / cytology
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Models, Molecular
  • Molecular Structure
  • Protein Binding / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship
  • Up-Regulation / genetics

Substances

  • 14-3-3 Proteins
  • RNA, Messenger
  • Small Molecule Libraries
  • Matrix Metalloproteinase 1