2-oxoglutarate analogue inhibitors of HIF prolyl hydroxylase.
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.
Mole
David R
DR
Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
Schlemminger
Imre
I
McNeill
Luke A
LA
Hewitson
Kirsty S
KS
Pugh
Christopher W
CW
Ratcliffe
Peter J
PJ
Schofield
Christopher J
CJ
D002384:Catalysis; D002474:Cell-Free System; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007501:Iron / Q000737:chemistry; D007502:Iron Chelating Agents / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007656:Ketoglutaric Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D014157:Transcription Factors / Q000378:metabolism*
D004791:Enzyme Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007502:Iron Chelating Agents; D007527:Isoenzymes; D007656:Ketoglutaric Acids; D014157:Transcription Factors; D007501:Iron; D011393:Procollagen-Proline Dioxygenase