6QGV

HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with a Spiro[4.5]decanone inhibitor (JPHM-2-167)

Summary for 6QGV

• Entry DOI: 10.2210/pdb6qgv/pdb
• Descriptor: Egl nine homolog 1, MANGANESE (II) ION, 8-[(3-methylpyridin-2-yl)methyl]-3-(4-phenylphenyl)-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decane-2,4-dione, ... (7 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: 1
• Total formula weight: 26940.42

Authors

Chowdhury, R.,Holt-Martyn, J.P.,Rahman, M.Z.,Schofield, C.J. (deposition date: 2019-01-13, release date: 2020-02-05, Last modification date: 2024-01-24)

Primary citation

Holt-Martyn, J.P.,Tumber, A.,Rahman, M.Z.,Lippl, K.,Figg Jr., W.,McDonough, M.A.,Chowdhury, R.,Schofield, C.J.
Studies on spiro[4.5]decanone prolyl hydroxylase domain inhibitors.
Medchemcomm, 10:500-504, 2019

PubMed Abstract: The 2-oxoglutarate (2OG) dependent hypoxia inducible factor (HIF) prolyl hydroxylases (PHDs) are targets for treatment of anaemia and other ischaemia related diseases. PHD inhibitors are in clinical trials; however, the number of reported templates for PHD inhibition is limited. We report structure-activity relationship and crystallographic studies on spiro[4.5]decanone containing PHD inhibitors. Together with other studies, our results reveal spiro[4.5]decanones as useful templates for generation of potent and selective 2OG oxygenase inhibitors.

PubMed: 31057728
DOI: 10.1039/c8md00548f

Experimental method

X-RAY DIFFRACTION (1.4 Å)