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
1. Choueiri TK, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Michaelson MD, Appleman LJ, Thamake S, Perini RF et al.. (2021)
Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis.
Nat Med, 27 (5): 802-805. [PMID:33888901]
2. Hasanov E, Jonasch E. (2021)
MK-6482 as a potential treatment for von Hippel-Lindau disease-associated clear cell renal cell carcinoma.
Expert Opin Investig Drugs, 30 (5): 495-504. [PMID:33945366]
3. Xu R, Wang K, Rizzi JP, Huang H, Grina JA, Schlachter ST, Wang B, Wehn PM, Yang H, Dixon DD et al.. (2019)
3-[(1S,2S,3R)-2,3-Difluoro-1-hydroxy-7-methylsulfonylindan-4-yl]oxy-5-fluorobenzonitrile (PT2977), a Hypoxia-Inducible Factor 2α (HIF-2α) Inhibitor for the Treatment of Clear Cell Renal Cell Carcinoma.
J Med Chem, 62 (15): 6876-6893. [PMID:31282155]
4. (2021)
The HIF2α Inhibitor Belzutifan Shows Signs of Efficacy in Kidney Cancer.
Cancer Discov, 11 (6): 1319. [PMID:33931436]