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PHD inhibition enables the treatment of anaemia\/ischaemia\u2010related disease. The PHD inhibitor Molidustat is approved for the treatment of renal anaemia; it differs from other approved\/late\u2010stage PHD inhibitors in lacking a glycinamide side chain. The first reported crystal structures of Molidustat and IOX4 (a brain\u2010penetrating derivative) complexed with PHD2 reveal how their contiguous triazole, pyrazolone and pyrimidine\/pyridine rings bind at the active site. The inhibitors bind to the active\u2010site metal in a bidentate manner through their pyrazolone and pyrimidine nitrogens, with the triazole \u03c0\u2010\u03c0\u2010stacking with Tyr303 in the 2OG binding pocket. Comparison of the new structures with other PHD inhibitor complexes reveals differences in the conformations of Tyr303, Tyr310, and a mobile loop linking \u03b22\u2013\u03b23, which are involved in dynamic substrate binding\/product release.<\/jats:p>","DOI":"10.1002\/cmdc.202100133","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T04:11:34Z","timestamp":1617250294000},"page":"2082-2088","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Structural Basis of Prolyl Hydroxylase Domain Inhibition by Molidustat"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-2606","authenticated-orcid":false,"suffix":"Jr","given":"William D.","family":"Figg","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Oxford  12 Mansfield Road Oxford OX1 3TA 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