5V18
Structure of PHD2 in complex with 1,2,4-Triazolo-[1,5-a]pyridine
Summary for 5V18
| Entry DOI | 10.2210/pdb5v18/pdb |
| Related | 5V1B |
| Descriptor | Egl nine homolog 1, SULFATE ION, 4-([1,2,4]triazolo[1,5-a]pyridin-5-yl)benzonitrile, ... (5 entities in total) |
| Functional Keywords | hif prolylhydroxylase domain-2, inhibitor, momodentate binding, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor |
| Biological source | Homo sapiens (Human) |
| Cellular location | Cytoplasm : Q9GZT9 |
| Total number of polymer chains | 1 |
| Total formula weight | 27161.58 |
| Authors | Skene, R.J. (deposition date: 2017-03-01, release date: 2017-06-21, Last modification date: 2024-03-06) |
| Primary citation | Ahmed, S.,Ayscough, A.,Barker, G.R.,Canning, H.E.,Davenport, R.,Downham, R.,Harrison, D.,Jenkins, K.,Kinsella, N.,Livermore, D.G.,Wright, S.,Ivetac, A.D.,Skene, R.,Wilkens, S.J.,Webster, N.A.,Hendrick, A.G. 1,2,4-Triazolo-[1,5-a]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Binding Interaction. J. Med. Chem., 60:5663-5672, 2017 Cited by PubMed Abstract: Herein we describe the identification of 4-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}benzonitrile-based inhibitors of the hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme. These inhibitors were shown to possess a novel binding mode by X-ray crystallography, in which the triazolo N1 atom coordinates in a hitherto unreported monodentate interaction with the active site Fe ion, while the benzonitrile group accepts a hydrogen-bonding interaction from the side chain residue of Asn315. Further optimization led to potent PHD-1 inhibitors with good physicochemical and pharmacokinetic properties. PubMed: 28594552DOI: 10.1021/acs.jmedchem.7b00352 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.15 Å) |
Structure validation
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