tivozanib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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: 4.12
  • 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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.388 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.968 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 15.311 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 3.076 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.510 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 1.970 % High 1
herg hERG pIC50 4.855 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 2.999 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 6.982 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.270 % High 1
kinase-safety-class ABL1,ABL2,ACVR1B,ACVR2A,ACVR2B,ACVRL1,AKT1,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK19,CDK7,CDK9,CSF1R,CSK,DDR1,EGFR,EIF2AK3,EPHA2,EPHB1,EPHB4,ERBB2,ERBB4,FGFR1,FGFR4,FLT1,FLT3,FLT4,FYN,GAK,GRK2,GSK3B,INSR,IRAK1,IRAK3,IRAK4,ITK,JAK1,JAK2,KDR,KIT,LCK,LYN,MAP2K1,MAP3K1,MAP3K10,MAP3K11,MAP3K14,MAP3K21,MAP3K7,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK10,MAPK11,MAPK12,MAPK14,MAPK7,MAPK9,MARK4,MET,MINK1,MST1R,MTOR,NTRK1,NTRK2,NTRK3,PAK4,PDGFRB,PDK1,PDK2,PDK4,PIK3CA,PIK3CD,PIK3CG,PRKCD,PRKDC,PTK6,RET,RIPK3,SIK2,SIK3,SRC,STK10,STK33,SYK,TEK,TGFBR1,TNIK,TTK,TYRO3,ULK1,ULK2,YES1 104
kinase-selectivity-class ABL2,ACVR2B,ALK,AURKA,AURKB,AURKC,AXL,BLK,BMX,BRAF,CDK9,CSF1R,CSK,DDR1,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,ERBB4,FGFR1,FLT1,FLT3,FLT4,FYN,INSR,JAK1,KDR,KIT,LCK,LYN,MAP2K1,MAP3K11,MAP3K21,MAP4K1,MAP4K3,MAPK7,MARK4,MET,MINK1,MST1R,NTRK1,NTRK3,PDGFRB,PDK4,PLK4,RET,RIPK3,SIK2,SRC,STK10,STK33,SYK,TEK,TGFBR1,TNIK,TTK,TYRO3,ULK1,YES1 60
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 3.459 High 1
mh-clint Mouse hepatocyte intrinsic clearance 17.865 High 1
mppb Mouse plasma protein binding (% unbound) 0.300 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 3.828 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 0.690 % High 1
rh-clint Rat hepatocyte intrinsic clearance 9.162 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 4.500 % High 1
rppb Rat plasma protein binding (% unbound) 0.270 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 0.548 uM High 1

Approvals:

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

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

None

FDA Adverse Event Reporting System (Pediatric)

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
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:65207 vascular endothelial growth factor receptor antagonist
CHEBI has role CHEBI:68495 apoptosis inducer

Related Drugs by ATC class:

L01EK Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors 3 drugs
apatinibaxitinibfruquintinib

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

DiseaseRelationSNOMED_IDDOID
Renal cell carcinoma indication 702391001 DOID:4450




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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 11504365 Nov. 5, 2039 TREATMENT OF ADULTS WITH MODERATE HEPATIC IMPAIRMENT AND RELAPSED OR REFRACTORY ADVANCED RENAL CELL CARCINOMA FOLLOWING TWO OR MORE PRIOR SYSTEMIC ANTI-CANCER THERAPIES WITH 1MG TIVOZANIB HCL ORALLY FOR 21 DAYS FOLLOWED BY NO DRUG FOR 7 DAYS

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
Proto-oncogene tyrosine-protein kinase Src Kinase IC50 6.02 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 5.66 CHEMBL
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
Angiopoietin-1 receptor Kinase IC50 7.11 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
Mitogen-activated protein kinase 3 Kinase IC50 9.89 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
ATP-binding cassette sub-family G member 2 Transporter IC50 7.16 CHEMBL
Mitogen-activated protein kinase 1 Kinase IC50 9.74 CHEMBL
Protein-tyrosine kinase 6 Kinase Kd 6.10 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 Cytosolic other 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
Ephrin type-B receptor 4 Kinase Kd 6.51 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 6.71 CHEMBL
Breakpoint cluster region protein Kinase Kd 6.80 CHEMBL

External reference:

IDSource
172030934T UNII
4040292 VANDF
C2827667 UMLSCUI
CHEBI:91327 CHEBI
AV9 PDB_CHEM_ID
CHEMBL1289494 ChEMBL_ID
9911830 PUBCHEM_CID
DB11800 DRUGBANK_ID
CHEMBL2105756 ChEMBL_ID
D09683 KEGG_DRUG
9203 INN_ID
C553176 MESH_SUPPLEMENTAL_RECORD_UI
6058 IUPHAR_LIGAND_ID
1179090001 SNOMEDCT_US
738747006 SNOMEDCT_US
763513002 SNOMEDCT_US
287483 MMSL
34747 MMSL
d08860 MMSL
017888 NDDF
2534233 RXNORM

Pharmaceutical products:

None