1. Academic Validation
  2. Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases

Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases

  • ACS Chem Biol. 2013 Jul 19;8(7):1488-96. doi: 10.1021/cb400088q.
Rasheduzzaman Chowdhury 1 José Ignacio Candela-Lena Mun Chiang Chan David Jeremy Greenald Kar Kheng Yeoh Ya-Min Tian Michael A McDonough Anthony Tumber Nathan R Rose Ana Conejo-Garcia Marina Demetriades Sinnakaruppan Mathavan Akane Kawamura Myung Kyu Lee Freek van Eeden Christopher W Pugh Peter J Ratcliffe Christopher J Schofield
Affiliations

Affiliation

  • 1 Department of Chemistry, Chemistry Research Laboratory, University of Oxford , Mansfield Road, Oxford, OX1 3TA, United Kingdom.
Abstract

The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in Animals. The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, we describe biochemical, crystallographic, cellular profiling, and animal studies on PHD inhibitors including selectivity studies using a representative set of human 2OG oxygenases. We identify suitable probe compounds for use in studies on the functional effects of PHD inhibition in cells and in Animals.

Figures