Chetomin, targeting HIF-1α/p300 complex, exhibits antitumour activity in multiple myeloma

Br J Cancer. 2016 Mar 1;114(5):519-23. doi: 10.1038/bjc.2016.20. Epub 2016 Feb 11.

Abstract

Background: Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. The constitutive expression of HIF-1α in MM suggests that inhibition of HIF-1α-mediated transcription represents an interesting target in MM.

Methods: As p300 is a crucial co-activator of hypoxia-inducible transcription, disrupting the complex HIF-1α/p300 to target HIF activity appears to be an attractive strategy.

Results: We reported that chetomin, an inhibitor of HIF-1α/p300 interaction, exhibits antitumour activity in human myeloma cell lines and primary MM cells from patients.

Conclusions: Our data suggest that chetomin may be of clinical value in MM and especially for patients characterised by a high EP300/HIF-1α expression and a poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Disulfides / pharmacology*
  • Drug Screening Assays, Antitumor
  • E1A-Associated p300 Protein / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Indole Alkaloids / pharmacology*
  • Molecular Targeted Therapy
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics
  • Prognosis

Substances

  • Disulfides
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Indole Alkaloids
  • chetomin
  • E1A-Associated p300 Protein
  • EP300 protein, human