ZG-2686 is a potent and selective HIF-2α agonist with an EC 50 of 0.25 µM. ZG-2686 exhibits selectivity over PHD2. ZG-2686 binds to a specific internal cavity of HIF-2α, forming hydrogen bonds via structural water molecules, which stabilizes the HIF-2α/ β heterodimer and enhances transcriptional activity. ZG-2686 synergizes with Vadadustat to upregulate HIF-2α-dependent EPO gene expression both in vitro and in vivo. ZG-2686 can be used for the research of renal anemia [1].
In Vivo, ZG-2686 (10 and 20 mg/kg; i.p.; single dose) shows limited in vivo EPO induction alone but synergizes with Vadadustat to enhance EPO expression in C57BL/6 mice[1].
In Vitro, ZG-2686 demonstrates good in vitro metabolic stability in rat plasma and liver microsomes[1]. ZG-2686 (10-20 μM; 12 h) shows a synergistic upregulation of HIF-2α-dependent EPO mRNA level in Hep3B cells when combined with Vadadustat[1].
References:
[1]. Gao Y, et al. Discovery of 3-(Arylamido)pyrazolopyridine HIF-2α Agonists and a Codrug Strategy with Prolyl Hydroxylase Inhibition for Synergistic Treatment of Renal Anemia. J Med Chem. 2025;68(23):25569-25589.
In Vivo, ZG-2686 (10 and 20 mg/kg; i.p.; single dose) shows limited in vivo EPO induction alone but synergizes with Vadadustat to enhance EPO expression in C57BL/6 mice[1].
In Vitro, ZG-2686 demonstrates good in vitro metabolic stability in rat plasma and liver microsomes[1]. ZG-2686 (10-20 μM; 12 h) shows a synergistic upregulation of HIF-2α-dependent EPO mRNA level in Hep3B cells when combined with Vadadustat[1].
References:
[1]. Gao Y, et al. Discovery of 3-(Arylamido)pyrazolopyridine HIF-2α Agonists and a Codrug Strategy with Prolyl Hydroxylase Inhibition for Synergistic Treatment of Renal Anemia. J Med Chem. 2025;68(23):25569-25589.