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 [4]. 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.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

belzutifan is commercially available from our sponsors

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
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
InChI Key LOMMPXLFBTZENJ-ZACQAIPSSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
MK-6482 progressed through 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 [2,5], 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.
NCT02974738 A Trial of PT2977 Tablets In Patients With Advanced Solid Tumors Phase 1 Interventional Peloton Therapeutics, Inc. 1
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. The LITESPARK-004 study; data were analysed for the CNS haemangioblastomas subgroup, with an additional 16 months of follow-up [3]. 3