Combining ligand- and structure-based approaches for the discovery of new inhibitors of the EPHA2-ephrin-A1 interaction

J Chem Inf Model. 2014 Oct 27;54(10):2621-6. doi: 10.1021/ci5004619. Epub 2014 Oct 7.

Abstract

The EPH receptor A2 (EPHA2) represents an attractive anticancer target. With the aim to identify novel EPHA2 receptor antagonists, a virtual screening campaign, combining shape-similarity and docking calculations, was conducted on a set of commercially available compounds. A combined score, taking into account both ligand- and structure-based results, was then used to identify the most promising candidates. Two compounds, selected among the best-ranked ones, were identified as EPHA2 receptor antagonists with micromolar affinity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Binding Sites
  • Butyrates / chemistry*
  • Cholic Acids / chemistry*
  • Drug Discovery*
  • Ephrin-A1 / antagonists & inhibitors*
  • Ephrin-A1 / chemistry
  • High-Throughput Screening Assays
  • Humans
  • Ligands
  • Molecular Docking Simulation
  • Naphthalenes / chemistry*
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry*
  • Receptor, EphA2 / antagonists & inhibitors*
  • Receptor, EphA2 / chemistry
  • Structure-Activity Relationship
  • User-Computer Interface

Substances

  • 4-(4-cyclopentylnaphthalen-1-yl)-4-oxobutanoic acid
  • Antineoplastic Agents
  • Butyrates
  • Cholic Acids
  • Ephrin-A1
  • Ligands
  • Naphthalenes
  • Protein Kinase Inhibitors
  • 3 beta-hydroxy-delta 5-cholenic acid
  • Receptor, EphA2