Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors

Eur J Med Chem. 2012 Mar;49:24-40. doi: 10.1016/j.ejmech.2012.01.033. Epub 2012 Jan 24.


Tumor hypoxia has been recognized as a common feature of solid tumors and a negative prognostic factor for response to treatment and survival of cancer patients. The discovery of hypoxia-inducible factor-1 (HIF-1), a molecular determinant of responses to hypoxia in mammalian cells, has renewed enthusiasm for discovery and development of targeted therapies exploiting the hypoxic tumor microenvironment. HIF-1 activity in tumors depends on availability of the HIF-1α subunit, the levels of which increase under hypoxic conditions and through activation of oncogenes and/or inactivation of tumor suppressor genes. Increased HIF-1 has been correlated with increased angiogenesis, aggressive tumor growth, and poor patient prognosis, leading to current interest in HIF-1 as promising anticancer drug target. In spite of an ever increasing number of putative small molecule inhibitors of HIF-1, only a few are progressing through preclinical and early clinical development. In this review, we will discuss recent advances in discovery and development of small molecule inhibitors that target the HIF-1 pathway as potential anticancer agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Drug Discovery
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1 / antagonists & inhibitors*
  • Hypoxia-Inducible Factor 1 / chemistry
  • Hypoxia-Inducible Factor 1 / genetics
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Models, Molecular
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*
  • Small Molecule Libraries / therapeutic use


  • Antineoplastic Agents
  • Hypoxia-Inducible Factor 1
  • Small Molecule Libraries