Table 2.
Pharmacological characteristics and current knowledge status of different Hypoxia-inducible factor prolyl hydroxylase inhibitors.
| Roxadustat (FBG-4592) | Vadadustat (AKB-6548) | Daprodustat (GSK 1278863) | Molidustat (BAY-3934) | |
|---|---|---|---|---|
| Affinity IC50 (uM) | 0.027 | 0.029 | 0.067 | 0.007 |
| PHD Isoform Selectivity | PHD 1-3 | PHD 3>2 | PHD 2-3 | PHD 2 < 1 and 3 |
| HIFα selectivity | HIF1α and 2α | HIF2α > 1α | HIF1α and 2α | HIF1α and 2α |
| Inhibitory concen-tration IC 50 (μM) | >100 | 29 | 21 | 65 |
| Half life humans (h) | 12 | 4.5 | 4 | Not available |
| Current status of development | 2019 approval in Japan and China Phase III reported at ASN 2019 | Ongoing phase III Preliminary report at ASN 2020 | Ongoing phase III | Completed phase II |
| Phase III clinical trials | DD (HD/DP) and NDD Correction and maintenance | DD (HD/DP) and NDD Correction and maintenance | DD (HD/DP) and NDD Correction and maintenance | Not available |
IC50, half maximal receptor inhibitory concentration; PHD, prolyl hydroxylase domain protein; HIF, hypoxia-inducible factor; ASN, American Society of Nephrology; DD, Dialysis Dependent; HD, Hemodialysis; DP, Peritoneal dialysis; NDD, Non-dialysis dependent.