title: 2-oxoglutarate analogue inhibitors of HIF prolyl hydroxylase.
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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Mole
authors.forename: Imre
authors.initials: I
authors.lastname: Schlemminger
authors.forename: Luke A
authors.initials: LA
authors.lastname: McNeill
authors.forename: Kirsty S
authors.initials: KS
authors.lastname: Hewitson
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Pugh
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ratcliffe
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Schofield
mesh_terms: 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*
chemical_list: 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