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. 2019 Dec 3;15(3):270–273. doi: 10.1002/cmdc.201900557

Figure 1.

Figure 1

HIF prolyl hydroxylases are therapeutic targets. A. Prolyl‐4‐hydroxylation of hypoxia inducible factor α (HIFα) subunits signals for their degradation via the ubiquitin proteasome system. 2OG, 2‐oxoglutarate; Suc, succinate; PHD1‐3, human prolyl hydroxylase enzymes 1–3; VHL−E3 ligase, the von Hippel‐Lindau protein (VHL) is the targeting component of a ubiquitin E3 ligase system. B. Examples of PHD inhibitors. Roxadustat (FG‐4592, 1), Daprodustat (GSK1278863, 2), Vadadustat (3), FG‐2216 (4) and Molidustat (BAY 85‐3924, 5). Representative 4‐hydroxypyrimidine (8) and spiro[4.5]decanone (18) inhibitors are shown, the biaryl unit of the latter binds in a hydrophobic pocket close to the PHD active site.