Roxadustat-d₅is intended for use as an internal standard for the quantification of roxadustat by GC- or LC-MS. Roxadustat is an inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH; IC₅₀s = 1.4, 1.26, and 1.32 µM for HIF-PH1, HIF-PH2, and HIF-PH3, respectively).¹It is selective for HIF-PH over other 2-oxoglutarate-dependent dioxygenases, including lysine-specific demethylase 5A (KDM5A), KDM5B, -5C, -5D, and -6B (IC₅₀s = >100 µM for all). Roxadustat (10-200 µM) stabilizes HIF-1α and HIF-2α in Hep3B hepatocellular carcinoma cells. It increases levels of secreted erythropoietin in Hep3B cells in a concentration-dependent manner and increases erythropoiesis in rats when administered at doses of 25 and 50 mg/kg.²Roxadustat reverses anemia in a rat model of chronic inflammation induced by peptidoglycan-polysaccharide, as well as a rat model of chronic kidney disease induced by 5/6 nephrectomy. It reduces tumor growth and increases survival in a murine Lewis lung carcinoma model when administered at a dose of 3 mg/animal.³

1.Yeh, T.-L., Leissing, T.M., Abboud, M.I., et al.Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trialsChem. Sci.8(11)7651-7668(2017) 2.Del Balzo, U., Signore, P.E., Walkinshaw, G., et al.Nonclinical characterization of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat, a novel treatment of anemia of chronic kidney diseaseJ. Pharmacol. Exp. Ther.374(4)342-353(2020) 3.Nishide, S., Matsunaga, S., Shiota, M., et al.Controlling the phenotype of tumor-infiltrating macrophages via the PHD-HIF axis inhibits tumor growth in a mouse modeliScience19940-954(2019)