ZG-2033 is an agonist of hypoxia-inducible factor 2α (HIF-2α).1 It induces HIF-2α transcriptional activity in a reporter assay using 786-O cells expressing HIF-2α (EC50 = 0.49 ?M). ZG-2033 (10 or 50 ?M), in combination with the inhibitor of hypoxia-inducible factor prolyl hydroxylase 2 (HIF-PH2) and HIF-PH3 AKB-6548 (vadadustat, increases the number of erythrocytes in a zebrafish model of doxorubicin-induced anemia. It increases the plasma levels of erythropoietin (EPO) in mice when administered at concentrations of 100 or 200 mg/kg in combination with vadadustat.
References:
[1]. Yu, Y., Yang, F., Yu, Q., et al.Discovery of a potent and orally bioavailable hypoxia-inducible factor 2α (HIF-2α) agonist and its synergistic therapy with prolyl hydroxylase inhibitors for the treatment of renal anemiaJ. Med. Chem.64(23)17384-17402(2021).