Belzutifan

Belzutifan is an inhibitor of hypoxia-inducible factor-2alpha (HIF-2alpha). It inhibits HIF-2alpha heterodimerization with the aryl hydrocarbon receptor nuclear translocator (ARNT) PAS-B domain in a cell-free assay (Ki = 23 nM), activation of HIF-2alpha in a reporter assay using 786-O renal cell carcinoma cells (IC50 = 17 nM), and secretion of the HIF-2alpha 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. 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. Formulations containing belzutifan have been used in the treatment of VHL disease-associated cancers.Formal Name: 3-[[(1S,2S,3R)-2,3-difluoro-2,3-dihydro-1-hydroxy-7-(methylsulfonyl)-1H-inden-4-yl]oxy]-5-fluoro-benzonitrile. CAS Number: 1672668-24-4. Synonyms: MK-6482, PT2977. Molecular Formula: C17H12F3NO4S. Formula Weight: 383.3. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Soluble, DMSO: Soluble. SMILES: CS(=O)(C1=C2C([C@H]([C@H]([C@H]2O)F)F)=C(C=C1)OC3=CC(F)=CC(C#N)=C3)=O. InChi Code: InChI=1S/C17H12F3NO4S/c1-26(23,24)12-3-2-11(13-14(12)17(22)16(20)15(13)19)25-10-5-8(7-21)4-9(18)6-10/h2-6,15-17,22H,1H3/t15-,16-,17+/m1/s1. InChi Key: LOMMPXLFBTZENJ-ZACQAIPSSA-N.