All FDA-approved EMA-approved PMDA-approved
Target Card Uniprot Example: P23975

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

Stem definition	Drug id	CAS RN
angiogenesis inhibitors	5258	475108-18-0

Description:

Molecule

Description

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:

Dose	Unit	Route
1	mg	O

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Property	Description	Value	Unit	Confidence	Similarity
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:

Date	Agency	Company	Orphan
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:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID	DOID
Renal cell carcinoma	indication	702391001	DOID:4450

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	10.87	acidic
pKa2	12.3	acidic
pKa3	4.95	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent 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 strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 0.89MG BASE	FOTIVDA	AVEO PHARMS	N212904	March 10, 2021	RX	CAPSULE	ORAL	March 10, 2026	NEW CHEMICAL ENTITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Vascular endothelial growth factor receptor 1	Kinase	P17948	VGFR1_HUMAN	INHIBITOR	IC50	9.68		SCIENTIFIC LITERATURE	DRUG LABEL
Vascular endothelial growth factor receptor 2	Kinase	P35968	VGFR2_HUMAN	INHIBITOR	IC50	9.80		SCIENTIFIC LITERATURE	DRUG LABEL
Vascular endothelial growth factor receptor 3	Kinase	P35916	VGFR3_HUMAN	INHIBITOR	IC50	9.62		SCIENTIFIC LITERATURE	DRUG LABEL
Proto-oncogene tyrosine-protein kinase Src	Kinase	P12931	SRC_HUMAN		IC50	6.02		CHEMBL
Tyrosine-protein kinase Lck	Kinase	P06239	LCK_HUMAN		Kd	5.66		CHEMBL
Ephrin type-A receptor 2	Kinase	P29317	EPHA2_HUMAN		Kd	6.83		CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret	Kinase	P07949	RET_HUMAN		Kd	7.92		CHEMBL
Platelet-derived growth factor receptor alpha	Kinase	P16234	PGFRA_HUMAN		IC50	8.65		CHEMBL
Angiopoietin-1 receptor	Kinase	Q02763	TIE2_HUMAN		IC50	7.11		CHEMBL
Tyrosine-protein kinase Lyn	Kinase	P07948	LYN_HUMAN		Kd	5.70		CHEMBL
Serine/threonine-protein kinase 10	Kinase	O94804	STK10_HUMAN		Kd	5.33		CHEMBL
Abelson tyrosine-protein kinase 2	Kinase	P42684	ABL2_HUMAN		Kd	6.52		CHEMBL
Ephrin type-A receptor 5	Kinase	P54756	EPHA5_HUMAN		Kd	6.22		CHEMBL
Ephrin type-A receptor 4	Kinase	P54764	EPHA4_HUMAN		Kd	5.25		CHEMBL
Mitogen-activated protein kinase 3	Kinase	P27361	MK03_HUMAN		IC50	9.89		CHEMBL
Tyrosine-protein kinase FRK	Kinase	P42685	FRK_HUMAN		Kd	6.84		CHEMBL
Receptor-interacting serine/threonine-protein kinase 2	Kinase	O43353	RIPK2_HUMAN		Kd	6.10		CHEMBL
Epithelial discoidin domain-containing receptor 1	Kinase	Q08345	DDR1_HUMAN		Kd	6.72		CHEMBL
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN		IC50	7.16		CHEMBL
Mitogen-activated protein kinase 1	Kinase	P28482	MK01_HUMAN		IC50	9.74		CHEMBL
Protein-tyrosine kinase 6	Kinase	Q13882	PTK6_HUMAN		Kd	6.10		CHEMBL
Ephrin type-B receptor 2	Kinase	P29323	EPHB2_HUMAN		IC50	7.76		CHEMBL
Discoidin domain-containing receptor 2	Kinase	Q16832	DDR2_HUMAN		Kd	6.23		CHEMBL
Aurora kinase B	Kinase	Q96GD4	AURKB_HUMAN		Kd	5.81		CHEMBL
Ephrin type-B receptor 3	Kinase	P54753	EPHB3_HUMAN		Kd	5.26		CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2	Kinase	Q12851	M4K2_HUMAN		Kd	5.62		CHEMBL
Receptor-interacting serine/threonine-protein kinase 3	Kinase	Q9Y572	RIPK3_HUMAN		Kd	5.87		CHEMBL
Phosphatidylethanolamine-binding protein 1	Cytosolic other	P30086	PEBP1_HUMAN		Kd	8.52		CHEMBL
Platelet-derived growth factor receptor beta	Kinase	P09619	PGFRB_HUMAN	INHIBITOR	IC50	8.76		SCIENTIFIC LITERATURE
Mast/stem cell growth factor receptor Kit	Kinase	P10721	KIT_HUMAN	INHIBITOR	IC50	8.79		SCIENTIFIC LITERATURE
Receptor-type tyrosine-protein kinase FLT3	Kinase	P36888	FLT3_HUMAN	INHIBITOR	IC50	6.38		SCIENTIFIC LITERATURE
Hepatocyte growth factor receptor	Kinase	P08581	MET_HUMAN	INHIBITOR	IC50	5.87		SCIENTIFIC LITERATURE
Fibroblast growth factor receptor 1	Kinase	P11362	FGFR1_HUMAN	INHIBITOR	IC50	6.52		SCIENTIFIC LITERATURE
Ephrin type-B receptor 4	Kinase	P54760	EPHB4_HUMAN		Kd	6.51		CHEMBL
Tyrosine-protein kinase ABL1	Kinase	P00519	ABL1_HUMAN		Kd	6.71		CHEMBL
Breakpoint cluster region protein	Kinase	P11274	BCR_HUMAN		Kd	6.80		CHEMBL

External reference:

ID	Source
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