The HIF pathway as a therapeutic target

Drug Discov Today. 2004 Aug 15;9(16):704-11. doi: 10.1016/S1359-6446(04)03202-7.

Abstract

Hypoxia-inducible factor (HIF) is an alpha,beta-heterodimeric transcription factor that mediates cellular responses to low oxygen concentration via the transcriptional activation of specific genes involved in both tumorogenesis and angiogenesis. Manipulation of the HIF pathway has potential use for the treatment of ischemic disease and cancer. Unlike HIF-beta, which is constitutively expressed, the levels and activity of the HIF-alpha subunit are regulated by processes involving posttranslational hydroxylation, catalyzed by Fe(II)- and 2-oxoglutarate-dependent oxygenases. This review focuses on the HIF pathway as a therapeutic target.

Publication types

  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Down-Regulation
  • Helix-Loop-Helix Motifs
  • Humans
  • Hydroxylation
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ischemia / metabolism
  • Ischemia / therapy
  • Neoplasms / blood supply
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Protein Subunits
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / metabolism*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism*
  • Up-Regulation

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Protein Subunits
  • Trans-Activators
  • Transcription Factors
  • endothelial PAS domain-containing protein 1