Identification of HSP60 as a primary target of o-carboranylphenoxyacetanilide, an HIF-1alpha inhibitor

J Am Chem Soc. 2010 Sep 1;132(34):11870-1. doi: 10.1021/ja104739t.

Abstract

We succeeded in the design and synthesis of multifunctional chemical probes of the HIF-1alpha inhibitor carboranylphenoxyacetanilide (1) that combine photoaffinity labeling and click reaction to identify the target protein. HSP60 was identified as a primary target protein of 1 using the chemical probes 2 and 3. Furthermore, HSP60 inhibitor 4 suppressed hypoxia-induced HIF activation, indicating that HSP60 affects HIF-1alpha accumulation directly or indirectly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / chemical synthesis
  • Acetanilides / chemistry
  • Acetanilides / pharmacology*
  • Boron Compounds / chemical synthesis
  • Boron Compounds / chemistry
  • Boron Compounds / pharmacology*
  • Chaperonin 60 / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Drug Design
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Molecular Probes / chemical synthesis
  • Molecular Probes / chemistry
  • Molecular Probes / pharmacology*
  • Molecular Structure
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Acetanilides
  • Boron Compounds
  • Chaperonin 60
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Molecular Probes