产品描述:
Belzutifan is an inhibitor of hypoxia-inducible factor-2α (HIF-2α).{69565,69566} It inhibits HIF-2α heterodimerization with the aryl hydrocarbon receptor nuclear translocator (ARNT) PAS-B domain in a cell-free assay (Ki = 23 nM), activation of HIF-2α in a reporter assay using 786-O renal cell carcinoma cells (IC50 = 17 nM), and secretion of the HIF-2α target VEGF-A from 786-O cells (EC50 = 17 nM). Belzutifan (0.3-3 mg/kg) induces tumor regression in a 786-O mouse xenograft model.{69566} It reduces hematocrit levels and right ventricular pressure in mice expressing an arginine-to-tryptophan mutation at position 200 in the von Hippel-Lindau protein (VHLR200W) in a model of Chuvash polycythemia when administered at a dose of 0.1 mg/g.{69567} Formulations containing belzutifan have been used in the treatment of VHL disease-associated cancers.