PT-2385 is a selective HIF-2α antagonist with a Ki of less than 50 nM.
PT-2385 (PT2385) is a selective antagonist of HIF-2 over HIF-1. PT-2385 is inactive for HIF-1α[1].
PT-2385 (PT2385) inhibits expression of HIF-2α regulated genes in a dose dependent manner in vivo. Tumor is regressed with PT-2385 (3 and 10 mg/kg, p.o., b.i.d. dose) in 786-O xenograft. PT-2385 (1,3 and 10 mg/kg) also inhibits tumor-derived VEGFA protein levels. PT-2385 (10 mg/kg) treatment reduces proliferation (Ki67) and angiogenesis (CD-31)[1].
[1]. Eli Wallace, Ph.D. PT2385: HIF-2α Antagonist for the Treatment of VHL Mutant ccRCC. 12th International VHL Medical Symposium April 8, 2016. [2]. Xie C, et al. Activation of intestinal hypoxia-inducible factor 2α during obesity contributes to hepatic steatosis. Nat Med. 2017 Nov;23(11):1298-1308.