Belzutifan CAS# 1672668-24-4 3-[[(1S,2S,3R)-2,3-二氟-2,3-二氢-1-羟基-7-(甲基磺酰基)-1H-茚-4-基]氧基]-5-氟苄腈

Belzutifan (MK-6482, PT2977) is a selective, orally bioavailable inhibitor of hypoxia-inducible factor-2α (HIF-2α). In preclinical studies, belzutifan bound HIF-2α with high affinity (Kd ~50 nM) and disrupted HIF-2α/HIF-1β dimerization, leading to suppression of downstream target genes such as VEGFA and EPO. In von Hippel–Lindau (VHL)-deficient renal cell carcinoma xenograft models, belzutifan reduced tumor growth by up to 70% and significantly inhibited angiogenesis. Pharmacokinetic studies in rodents and primates demonstrated good oral bioavailability (~40–60%) and dose-dependent plasma exposure. Collectively, these data supported belzutifan’s advancement into clinical development for VHL-associated and sporadic clear cell renal cell carcinoma.