belzutifan 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
5469 1672668-24-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • belzutifan
  • welireg
  • MK-6482
  • PT2977
Belzutifan is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2alpha), with potential antineoplastic activity. HIF-2alpha is a transcription factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia. Under normal oxygen levels, HIF-2alpha is targeted for ubiquitin-proteasomal degradation by VHL protein. Lack of functional VHL protein results in stabilization and accumulation of HIF-2alpha. Upon stabilization, HIF-2alpha translocates into the nucleus and interacts with hypoxia-inducible factor 1 beta (HIF-1beta) to form a transcriptional complex that induces expression of downstream genes, including genes associated with cellular proliferation, angiogenesis, and tumor growth. Belzutifan binds to HIF-2alpha, and in conditions of hypoxia or impairment of VHL protein function, belzutifan blocks the HIF-2alpha-HIF-1beta interaction, leading to reduced transcription and expression of HIF-2alpha target genes. In vivo, belzutifan demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma.
  • Molecular weight: 383.34
  • Formula: C17H12F3NO4S
  • CLOGP: 1.55
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 87.39
  • ALOGS: -3.68
  • ROTB: 3
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Aug. 13, 2021 FDA MERCK SHARP DOHME

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Anaemia 74.58 54.81 26 107 293404 63195485
Hypoxia 62.71 54.81 16 117 59776 63429113

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hypoxia 82.30 58.03 23 140 55072 34901696

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hypoxia 126.50 55.15 36 290 103207 79640855
Anaemia 107.57 55.15 46 280 444969 79299093

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01XX74 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
MeSH PA D000970 Antineoplastic Agents
FDA MoA N0000185506 Cytochrome P450 3A4 Inducers
FDA MoA N0000193998 Hypoxia-inducible Factor 2 alpha Inhibitors
FDA EPC N0000193999 Hypoxia-inducible Factor Inhibitor

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Von Hippel-Lindau (VHL) disease indication 46659004 DOID:14175




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
40MG WELIREG MERCK SHARP DOHME N215383 Aug. 13, 2021 RX TABLET ORAL 9908845 Sept. 5, 2034 TREATMENT OF ADULT PATIENTS WITH VON HIPPEL-LINDAU DISEASE WHO REQUIRE THERAPY FOR ASSOCIATED RENAL CELL CARCINOMA, CENTRAL NERVOUS SYSTEM HEMANGIOBLASTOMAS, OR PANCREATIC NEUROENDOCRINE TUMORS, NOT REQUIRING IMMEDIATE SURGERY
40MG WELIREG MERCK SHARP DOHME N215383 Aug. 13, 2021 RX TABLET ORAL 9969689 Sept. 5, 2034 TREATMENT OF ADULT PATIENTS WITH VON HIPPEL-LINDAU DISEASE WHO REQUIRE THERAPY FOR ASSOCIATED RENAL CELL CARCINOMA, CENTRAL NERVOUS SYSTEM HEMANGIOBLASTOMAS, OR PANCREATIC NEUROENDOCRINE TUMORS, NOT REQUIRING IMMEDIATE SURGERY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
40MG WELIREG MERCK SHARP DOHME N215383 Aug. 13, 2021 RX TABLET ORAL Aug. 13, 2026 NEW CHEMICAL ENTITY
40MG WELIREG MERCK SHARP DOHME N215383 Aug. 13, 2021 RX TABLET ORAL Aug. 13, 2028 TREATMENT OF ADULT PATIENTS WITH VON HIPPEL-LINDAU (VHL) DISEASE WHO REQUIRE THERAPY FOR ASSOCIATED RENAL CELL CARCINOMA (RCC), CENTRAL NERVOUS SYSTEM (CNS) HEMANGIOBLASTOMAS, OR PANCREATIC NEUORENDOCRINE TUMORS (PNET), NOT REQUIRING IMMEDIATE SURGERY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Endothelial PAS domain-containing protein 1 Transcription factor INHIBITOR IC50 8 DRUG LABEL DRUG LABEL

External reference:

IDSource
7K28NB895L UNII
C5418188 UMLSCUI
72Q PDB_CHEM_ID
CHEMBL4585668 ChEMBL_ID
D11954 KEGG_DRUG
117947097 PUBCHEM_CID
DB15463 DRUGBANK_ID
11196 INN_ID
11251 IUPHAR_LIGAND_ID
018835 NDDF
4040773 VANDF
2567226 RXNORM
349651 MMSL
39823 MMSL
d09792 MMSL
C000720612 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
WELIREG HUMAN PRESCRIPTION DRUG LABEL 1 0006-5331 TABLET, FILM COATED 40 mg ORAL NDA 32 sections
WELIREG HUMAN PRESCRIPTION DRUG LABEL 1 0006-5331 TABLET, FILM COATED 40 mg ORAL NDA 32 sections