Old drug new tricks: Chlorhexidine acts as a potential allosteric inhibitor toward PAK1

Biochem Biophys Res Commun. 2018 Jan 1;495(1):728-732. doi: 10.1016/j.bbrc.2017.11.087. Epub 2017 Nov 14.

Abstract

This paper describes the identification of chlorhexidine, an agent commonly used in clinical as a novel potential allosteric inhibitor of PAK1. In cellular assays, chlorhexidine showed a good inhibitory profile, and its inhibitory profile was even better than IPA-3, a well-known allosteric inhibitor. In pharmacology experiments, chlorhexidine successfully inhibited the relief of PAK1 dimer and inhibited the activation of PAK1. Our findings offer an insight for the new drug development of PAK1 inhibitor. We also provide a possible explanation for the phenomenon that the application of the chlorhexidine in peritoneal lavage inhibited the development of tumor.

Keywords: Allosteric inhibitor; Chlorhexidine; PAK1; Virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Binding Sites
  • Cell Line, Tumor
  • Chlorhexidine / administration & dosage*
  • Chlorhexidine / chemistry*
  • Humans
  • Molecular Docking Simulation
  • Molecular Targeted Therapy / methods
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism*
  • Neoplasms, Experimental / pathology
  • Protein Binding
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / chemistry
  • p21-Activated Kinases / chemistry*
  • p21-Activated Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • PAK1 protein, human
  • p21-Activated Kinases
  • Chlorhexidine