Vadadustat  (Synonyms: PG-1016548; AKB-6548)

Vadadustat (PG-1016548) is a titratable, oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor^[1]. Vadadustat is an erythropoiesis-stimulating agent and has the potential for anemia treatment in chronic kidney disease in vivo^[1][2].

IC50: HIF-PH^[1]

Vadadustat induces endogenous erythropoietin synthesis and enhances iron mobilization. Vadadustat is well-tolerated in healthy volunteers and patients with chronic kidney disease, where it increases reticulocytes, plasma EPO, and Hb levels in a dose-dependent manner. The increase in plasma EPO levels seen with vadadustat is comparable in magnitude to that occurring physiologically at moderate altitude and shows a normal diurnal pattern with a return to baseline levels prior to the next dose. Vadadustat improves iron homeostasis by decreasing hepcidin and increasing transferrin levels. once-daily oral administration of vadadustat, titrated to increase and maintain Hb in the target range, may provide multiple advantages over conventional ESAs^[1]. Vadadustat is observed to have a half-life of approximately 4.5 hours. Overall, patients demonstrate an increase in Hb levels, from 9.91 g/dL at baseline to 10.54 g/dL by day 29. Ferritin levels decrease from 334.1 ng/mL at baseline to 271.7 ng/mL by day 29^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

306.70

Solid

C₁₄H₁₁ClN₂O₄

1000025-07-9

O=C(O)CNC(C1=NC=C(C2=CC=CC(Cl)=C2)C=C1O)=O

Room temperature in continental US; may vary elsewhere.

• [1]. Pergola PE, et al. Vadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease. Kidney Int. 2016 Nov;90(5):1115-1122.  [Content Brief]

  [2]. Gupta N, et al. Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD. Am J Kidney Dis. 2017 Feb 24. pii: S0272-6386(17)30110-5.  [Content Brief]