6ST3

HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with 4-hydroxy-N-(4-phenoxybenzyl)-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamide

Summary for 6ST3

• Entry DOI: 10.2210/pdb6st3/pdb
• Descriptor: Egl nine homolog 1, 4-oxidanyl-~{N}-[(4-phenoxyphenyl)methyl]-2-pyrazol-1-yl-pyrimidine-5-carboxamide, FORMIC ACID, ... (5 entities in total)
• Functional Keywords: oxidoreductase, non-heme dioxygenase, iron, 2-oxoglutarate, hypoxia-inducible factor, hif, hif prolyl hydroxylase domain 2, phd2, egln1, oxygenase, hypoxia, dna-binding, metal-binding, transcription, helix-loop-helix-beta, dsbh, facial triad, cytoplasm, transcription/epigenetic regulation, signaling, development, cell structure, beta-hydroxylation, transcription activator/inhibitor, ubl conjugation, polymorphism, vitamin c, zinc-finger, familial erythrocytosis, breast cancer, transcription complex
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 53049.87

Authors

Chowdhury, R.,Holt-Martyn, J.P.,Schofield, C.J. (deposition date: 2019-09-10, release date: 2019-12-04, Last modification date: 2024-01-24)

Primary citation

Holt-Martyn, J.P.,Chowdhury, R.,Tumber, A.,Yeh, T.L.,Abboud, M.I.,Lippl, K.,Lohans, C.T.,Langley, G.W.,Figg Jr., W.,McDonough, M.A.,Pugh, C.W.,Ratcliffe, P.J.,Schofield, C.J.
Structure-Activity Relationship and Crystallographic Studies on 4-Hydroxypyrimidine HIF Prolyl Hydroxylase Domain Inhibitors.
Chemmedchem, 15:270-273, 2020

PubMed Abstract: The 2-oxoglutarate-dependent hypoxia inducible factor prolyl hydroxylases (PHDs) are targets for treatment of a variety of diseases including anaemia. One PHD inhibitor is approved for use for the treatment of renal anaemia and others are in late stage clinical trials. The number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on a promising class of 4-hydroxypyrimidine-containing PHD inhibitors.

PubMed: 31751494
DOI: 10.1002/cmdc.201900557

Experimental method

X-RAY DIFFRACTION (2.426 Å)