2-oxoglutarate analogue inhibitors of HIF prolyl hydroxylase

Bioorg Med Chem Lett. 2003 Aug 18;13(16):2677-80. doi: 10.1016/s0960-894x(03)00539-0.

Abstract

Hydroxylation of hypoxia-inducible factor, a nuclear transcription factor, is catalysed by iron and 2-oxoglutarate dependent hydroxylases. Various analogues of the 2-oxoglutarate cosubstrate were synthesised and shown to inhibit the activity of human hypoxia-inducible factor-1alpha prolyl hydroxylases in cell-free extracts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Cell-Free System
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Iron / chemistry
  • Iron Chelating Agents / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Ketoglutaric Acids / chemical synthesis*
  • Ketoglutaric Acids / pharmacology
  • Molecular Structure
  • Procollagen-Proline Dioxygenase / antagonists & inhibitors*
  • Transcription Factors / metabolism*

Substances

  • Enzyme Inhibitors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Iron Chelating Agents
  • Isoenzymes
  • Ketoglutaric Acids
  • Transcription Factors
  • Iron
  • Procollagen-Proline Dioxygenase