belzutifan   Click here for help

GtoPdb Ligand ID: 11251

Synonyms: compound 2 [PMID: 31282155] | MK-6482 | MK6482 | PT2977 | Welireg®
Approved drug PDB Ligand
belzutifan is an approved drug (FDA (2021))
Compound class: Synthetic organic
Comment: Belzutifan (previously PT2977 and MK-6482) binds to and inhibits HIF-2α function, and has been developed as a novel cancer therapeutic [3]. HIF-2α is a transcription factor component that is established as an oncogneic driver of ccRCC, via loss of its interaction with the tumour suppressor von Hippel-Lindau (VHL), which results in disrupted proteasomal degradation and thereby accumulation of HIF-2α. Elevated HIF-2α promotes increased expression of hypoxia-responsive genes which regulate processes including angiogenesis, proliferation, migration, and immune evasion.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 95.77
Molecular weight 383.04
XLogP 2.69
No. Lipinski's rules broken 0
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Canonical SMILES N#Cc1cc(cc(c1)F)Oc1ccc(c2c1[C@@H](F)[C@H]([C@H]2O)F)S(=O)(=O)C
Isomeric SMILES N#Cc1cc(cc(c1)F)Oc1ccc(c2c1[C@@H](F)[C@H]([C@H]2O)F)S(=O)(=O)C
InChI 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
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Summary of Clinical Use Click here for help
MK-6482 progressed though advanced clinical evaluation in patients with ccRCC and earlier phase trials in glioblastoma. In August 2021, the FDA approved belzutifan for adult patients with von Hippel-Lindau (VHL) disease, who have VHL-associated cancers (renal cell carcinoma [2,4], central nervous system hemangioblastomas, or pancreatic neuroendocrine tumours) that require therapy.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03634540 A Trial of PT2977 in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) Phase 2 Interventional Peloton Therapeutics, Inc.
NCT04195750 A Study of MK-6482 Versus Everolimus in Participants With Advanced Renal Cell Carcinoma (MK-6482-005) Phase 3 Interventional Merck Sharp & Dohme Corp.
NCT03401788 A Phase 2 Study of PT2977 for the Treatment of Von Hippel Lindau Disease-Associated Renal Cell Carcinoma Phase 2 Interventional Peloton Therapeutics, Inc.
NCT02974738 A Trial of PT2977 Tablets In Patients With Advanced Solid Tumors Phase 1 Interventional Peloton Therapeutics, Inc. 1