tivozanib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
angiogenesis inhibitors 5258 475108-18-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • tivozanib
  • tivozanib hydrochloride monohydrate
  • fotivda
  • Kil8951
  • AV-951
  • KRN951
Tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib is indicated as first line treatment of adult patients with advanced renal cell carcinoma (RCC) and for adult patients who are VEGFR and mTOR pathway inhibitor-naive following disease progression after one prior treatment with cytokine therapy for advanced RCC.
  • Molecular weight: 454.87
  • Formula: C22H19ClN4O5
  • CLOGP: 4.62
  • LIPINSKI: 0
  • HAC: 9
  • HDO: 2
  • TPSA: 107.74
  • ALOGS: -3.94
  • ROTB: 6

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
1 mg O

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
Aug. 24, 2017 EMA EUSA Pharma (UK) Limited
March 10, 2021 FDA AVEO PHARMACEUTICALS, Inc

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01EK03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors
FDA MoA N0000020001 Tyrosine Kinase Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Renal cell carcinoma indication 702391001 DOID:4450

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.87 acidic
pKa2 12.3 acidic
pKa3 4.95 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 0.89MG BASE FOTIVDA AVEO PHARMS N212904 March 10, 2021 RX CAPSULE ORAL 6821987 April 26, 2023 A METHOD OF TREATING ADULTS WITH RELAPSED OR REFRACTORY ADVANCED RENAL CELL CARCINOMA FOLLOWING TWO OR MORE PRIOR SYSTEMIC THERAPIES BY INHIBITING THE ANGIOGENESIS OF BLOOD VESSELS WITH A VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITOR

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 0.89MG BASE FOTIVDA AVEO PHARMS N212904 March 10, 2021 RX CAPSULE ORAL March 10, 2026 NEW CHEMICAL ENTITY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Vascular endothelial growth factor receptor 1 Kinase INHIBITOR IC50 9.68 SCIENTIFIC LITERATURE DRUG LABEL
Vascular endothelial growth factor receptor 2 Kinase INHIBITOR IC50 9.80 SCIENTIFIC LITERATURE DRUG LABEL
Vascular endothelial growth factor receptor 3 Kinase INHIBITOR IC50 9.62 SCIENTIFIC LITERATURE DRUG LABEL
Ephrin type-A receptor 2 Kinase Kd 6.83 CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase Kd 7.92 CHEMBL
Platelet-derived growth factor receptor alpha Kinase IC50 8.65 CHEMBL
Tyrosine-protein kinase Lyn Kinase Kd 5.70 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 5.33 CHEMBL
Abelson tyrosine-protein kinase 2 Kinase Kd 6.52 CHEMBL
Ephrin type-A receptor 5 Kinase Kd 6.22 CHEMBL
Ephrin type-A receptor 4 Kinase Kd 5.25 CHEMBL
Tyrosine-protein kinase FRK Kinase Kd 6.84 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 6.10 CHEMBL
Epithelial discoidin domain-containing receptor 1 Kinase Kd 6.72 CHEMBL
Ephrin type-B receptor 4 Kinase Kd 6.51 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 6.71 CHEMBL
Ephrin type-B receptor 2 Kinase IC50 7.76 CHEMBL
Discoidin domain-containing receptor 2 Kinase Kd 6.23 CHEMBL
Aurora kinase B Kinase Kd 5.81 CHEMBL
Ephrin type-B receptor 3 Kinase Kd 5.26 CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2 Kinase Kd 5.62 CHEMBL
Receptor-interacting serine/threonine-protein kinase 3 Kinase Kd 5.87 CHEMBL
Phosphatidylethanolamine-binding protein 1 Unclassified Kd 8.52 CHEMBL
Platelet-derived growth factor receptor beta Kinase INHIBITOR IC50 8.76 SCIENTIFIC LITERATURE
Mast/stem cell growth factor receptor Kit Kinase INHIBITOR IC50 8.79 SCIENTIFIC LITERATURE
Receptor-type tyrosine-protein kinase FLT3 Kinase INHIBITOR IC50 6.38 SCIENTIFIC LITERATURE
Hepatocyte growth factor receptor Kinase INHIBITOR IC50 5.87 SCIENTIFIC LITERATURE
Fibroblast growth factor receptor 1 Kinase INHIBITOR IC50 6.52 SCIENTIFIC LITERATURE
Protein-tyrosine kinase 6 Kinase Kd 6.10 CHEMBL
Breakpoint cluster region protein Kinase Kd 6.80 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 5.66 CHEMBL

External reference:

IDSource
172030934T UNII
4040292 VANDF
C2827667 UMLSCUI
AV9 PDB_CHEM_ID
CHEMBL1289494 ChEMBL_ID
9911830 PUBCHEM_CID
DB11800 DRUGBANK_ID
CHEMBL2105756 ChEMBL_ID
D09683 KEGG_DRUG
C553176 MESH_SUPPLEMENTAL_RECORD_UI
6058 IUPHAR_LIGAND_ID
9203 INN_ID
2534233 RXNORM
287483 MMSL
34747 MMSL
d08860 MMSL
017888 NDDF
738747006 SNOMEDCT_US
763513002 SNOMEDCT_US

Pharmaceutical products:

None