Compound Detail

CHEMBL1289494

TIVOZANIB

💊 Approved Drug

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💊 Approved Drug

COc1cc2nccc(Oc3ccc(NC(=O)Nc4cc(C)on4)c(Cl)c3)c2cc1OC

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1289494
Name	TIVOZANIB
Phase	Approved
Structure Type	MOL
InChI Key	SPMVMDHWKHCIDT-UHFFFAOYSA-N
Therapeutic	✓ Yes

Known Names

ASP-4130 AV-951 Kil-8951 KIL8951 Krn-951 Tivozanib

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

454.9

MW (Da)

5.64

ALogP

HBA

HBD

107.7

PSA (Å²)

0.39

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
First Approval	2017
Availability	Prescription
Chirality	Achiral

Routes of Administration

Oral

Flags

Natural Product

USAN Stem	-anib
USAN Year	2009

Extended Properties

Molecular Formula	C22H19ClN4O5
MW	454.87
Aromatic Rings	4
Heavy Atoms	32
NP-Likeness	-1.57

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Vascular endothelial growth factor receptor inhibitor	INHIBITOR	Vascular endothelial growth factor receptor	✓	✓

Indications

Carcinoma, Renal Cell Carcinoma, Renal Cell Neoplasms Carcinoma, Hepatocellular Colorectal Neoplasms Fallopian Tube Neoplasms Glioblastoma Ovarian Neoplasms Prostatic Neoplasms, Castration-Resistant Sarcoma Breast Neoplasms Carcinoma, Non-Small-Cell Lung Cholangiocarcinoma

ATC Classification

L01EK03

tivozanib

Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 48 meas. best 9.89

Kd 24 meas. best 8.52

Ki 1 meas. best 8.19

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Mitogen-activated protein kinase 3 CHEMBL3385	IC50	9.89	9.89	0.1	1
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	9.8	8.7429	0.2	7
Mitogen-activated protein kinase 1 CHEMBL4040	IC50	9.74	9.74	0.2	1
Vascular endothelial growth factor receptor 1 CHEMBL3516	IC50	9.68	9.68	0.2	1
Vascular endothelial growth factor receptor 1 CHEMBL1868	IC50	9.68	8.4667	0.2	3
Vascular endothelial growth factor receptor 3 CHEMBL1955	IC50	9.62	8.8925	0.2	4
HUVEC CHEMBL613979	IC50	9.17	9.17	0.7	1
Mast/stem cell growth factor receptor Kit CHEMBL1936	IC50	8.79	7.95	1.6	2
Platelet-derived growth factor receptor beta CHEMBL1913	IC50	8.76	8.035	1.7	2
Platelet-derived growth factor receptor alpha CHEMBL2007	IC50	8.65	8.025	2.3	2
Phosphatidylethanolamine-binding protein 1 CHEMBL4105856	Kd	8.52	8.52	3.0	1
Vascular endothelial growth factor receptor 2 CHEMBL279	Ki	8.19	8.19	6.5	1
Proto-oncogene tyrosine-protein kinase receptor Ret CHEMBL2041	Kd	7.92	7.92	12.0	1
Ephrin type-B receptor 2 CHEMBL3290	IC50	7.76	7.69	17.5	2
Broad substrate specificity ATP-binding cassette transporter ABCG2 CHEMBL5393	IC50	7.16	7.16	70.0	1
Angiopoietin-1 receptor CHEMBL4128	IC50	7.11	7.11	78.0	1
Tyrosine-protein kinase FRK CHEMBL4223	Kd	6.84	6.84	145.0	1
Ephrin type-A receptor 2 CHEMBL2068	Kd	6.83	6.83	147.0	1
Breakpoint cluster region protein CHEMBL5146	Kd	6.8	6.8	160.0	1
Epithelial discoidin domain-containing receptor 1 CHEMBL5319	Kd	6.72	6.72	190.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	Kd	6.71	6.71	195.0	1
Tyrosine-protein kinase ABL2 CHEMBL4014	Kd	6.52	6.52	302.0	1
Fibroblast growth factor receptor 1 CHEMBL3650	IC50	6.52	6.4	299.0	2
Ephrin type-B receptor 4 CHEMBL5147	Kd	6.51	6.51	310.0	1
MCF7 CHEMBL387	IC50	6.42	6.42	380.0	2
NCI-H460 CHEMBL396	IC50	6.41	6.41	390.0	1
Receptor-type tyrosine-protein kinase FLT3 CHEMBL1974	IC50	6.38	6.38	422.0	1
Ephrin type-B receptor 2 CHEMBL3290	Kd	6.35	6.35	448.0	1
Ephrin type-B receptor 4 CHEMBL5147	IC50	6.32	6.32	480.0	1
Hepatocyte growth factor receptor CHEMBL3717	IC50	6.26	6.065	550.0	2
Discoidin domain-containing receptor 2 CHEMBL5122	Kd	6.23	6.23	592.0	1
Ephrin type-A receptor 5 CHEMBL3987	Kd	6.22	6.22	601.0	1
A549 CHEMBL392	IC50	6.21	6.21	620.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	IC50	6.21	6.21	620.0	1
Protein-tyrosine kinase 6 CHEMBL4601	Kd	6.1	6.1	787.0	1
Receptor-interacting serine/threonine-protein kinase 2 CHEMBL5014	Kd	6.1	6.1	801.0	1
Proto-oncogene tyrosine-protein kinase Src CHEMBL267	IC50	6.02	6.02	960.0	1
Receptor-interacting serine/threonine-protein kinase 3 CHEMBL1795199	Kd	5.87	5.87	1346.0	1
Aurora kinase B CHEMBL2185	Kd	5.81	5.81	1562.0	1
Unchecked CHEMBL612545	IC50	5.79	5.3067	1622.8	6
Tyrosine-protein kinase Lyn CHEMBL3905	Kd	5.7	5.7	2019.0	1
Tyrosine-protein kinase Lck CHEMBL258	Kd	5.66	5.66	2183.0	1
Mitogen-activated protein kinase kinase kinase kinase 2 CHEMBL5330	Kd	5.62	5.62	2375.0	1
Platelet-derived growth factor receptor beta CHEMBL1913	Kd	5.62	5.62	2409.0	1
Serine/threonine-protein kinase 10 CHEMBL3981	Kd	5.33	5.33	4622.0	1
Hepatocyte growth factor receptor CHEMBL3717	Kd	5.27	5.27	5403.0	1
Ephrin type-B receptor 3 CHEMBL4901	Kd	5.26	5.26	5433.0	1
Ephrin type-A receptor 4 CHEMBL3988	Kd	5.25	5.25	5563.0	1
B16-F10 CHEMBL612656	IC50	4.73	4.73	18800.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	49147.0	ng.hr.mL-1	Rattus norvegicus
AUC	47453.0	ng.hr.mL-1	Rattus norvegicus
AUC	340.0	ng.hr.mL-1	Rattus norvegicus
AUC	1640.0	ng.hr.mL-1	Rattus norvegicus
AUC	7640.0	ng.hr.mL-1	Rattus norvegicus
AUC	44500.0	ng.hr.mL-1	Rattus norvegicus
Cmax	6731.59	nM	Rattus norvegicus
Cmax	47.49	nM	Rattus norvegicus
Cmax	237.43	nM	Rattus norvegicus
Cmax	1064.04	nM	Rattus norvegicus
Cmax	6206.17	nM	Rattus norvegicus
Cmax	272.61	nM	Rattus norvegicus
MRT	13.4	hr	Rattus norvegicus
T1/2	9.35	hr	Rattus norvegicus
T1/2	9.25	hr	Rattus norvegicus
T1/2	7.78	hr	Rattus norvegicus
T1/2	8.13	hr	Rattus norvegicus
T1/2	7.94	hr	Rattus norvegicus
Tmax	4.8	hr	Rattus norvegicus
Tmax	3.63	hr	Rattus norvegicus
Tmax	2.63	hr	Rattus norvegicus
Tmax	4.25	hr	Rattus norvegicus
Tmax	3.5	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Mitogen-activated protein kinase 3	IC50	=	0.13	nM	9.89	Inhibition of ERK1 phosphorylation in VEGF-stimulated serum-starved human HUVEC ...	16982756
Vascular endothelial growth factor receptor 2	IC50	=	0.16	nM	9.8	Inhibition of recombinant VEGFR2 after 1 hr by fluorescence polarization assay	20869793
Vascular endothelial growth factor receptor 2	IC50	=	0.16	nM	9.8	Inhibition of VEGFR2	23098265
Vascular endothelial growth factor receptor 2	IC50	=	0.16	nM	9.8	Inhibition of VEGFR-2 phosphorylation in serum starved human HUVEC cells incubat...	16982756
Mitogen-activated protein kinase 1	IC50	=	0.18	nM	9.74	Inhibition of ERK2 phosphorylation in VEGF-stimulated serum-starved human HUVEC ...	16982756
Vascular endothelial growth factor receptor 1	IC50	=	0.21	nM	9.68	Inhibition of VEGFR1	23098265
Vascular endothelial growth factor receptor 1	IC50	=	0.21	nM	9.68	Inhibition of VEGFR-1 phosphorylation in serum starved mouse NIH3T3 cells transf...	16982756
Vascular endothelial growth factor receptor 3	IC50	=	0.24	nM	9.62	Inhibition of VEGFR3	23098265
Vascular endothelial growth factor receptor 3	IC50	=	0.24	nM	9.62	Inhibition of VEGFR-3 phosphorylation in serum starved human HUVEC cells incubat...	16982756
HUVEC	IC50	=	0.67	nM	9.17	Antiproliferative activity against VEGF-induced human HUVEC cells assessed as ce...	16982756
Mast/stem cell growth factor receptor Kit	IC50	=	1.63	nM	8.79	Inhibition of c-Kit phosphorylation in serum starved human KU812 cell line incub...	16982756
Platelet-derived growth factor receptor beta	IC50	=	1.72	nM	8.76	Inhibition of PDGFR-beta phosphorylation in serum starved human NHDF cells incub...	16982756
Vascular endothelial growth factor receptor 2	IC50	=	2.14	nM	8.67	Inhibition of recombinant VEGFR2 (unknown origin) by cell-free assay	25908516
Platelet-derived growth factor receptor alpha	IC50	=	2.26	nM	8.65	Inhibition of recombinant PDGFRalpha (unknown origin) by cell-free assay	25908516
Phosphatidylethanolamine-binding protein 1	Kd	=	3.0	nM	8.52	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase ...	29191878
Vascular endothelial growth factor receptor 3	IC50	=	3.11	nM	8.51	Inhibition of recombinant VEGFR3 (unknown origin) by cell-free assay	25908516
Vascular endothelial growth factor receptor 2	IC50	=	3.38	nM	8.47	Inhibition of VEGFR-2 (unknown origin)	37453330
Vascular endothelial growth factor receptor 1	IC50	=	6.26	nM	8.2	Inhibition of recombinant VEGFR1 (unknown origin) by cell-free assay	25908516
Vascular endothelial growth factor receptor 2	Ki	=	6.5	nM	8.19	In-Vitro Kinase Inhibition Assay: Compounds 2-4 and cabozantinib were each teste...	-
Vascular endothelial growth factor receptor 2	IC50	=	6.5	nM	8.19	Inhibition of VEGFR-2 (unknown origin) in presence of ATP	16982756

Literature References

PubMed	DOI	Target Context	# Activities
16982756	10.1158/0008-5472.can-05-4290	ADMET	27
16982756	10.1158/0008-5472.can-05-4290	Calu-6	18
16982756	10.1158/0008-5472.can-05-4290	Unchecked	11
26254279	10.18632/oncotarget.4214	Unchecked	9
25908516	10.1016/j.bmcl.2015.03.088	Rattus norvegicus	6
16982756	10.1158/0008-5472.can-05-4290	A549	6
29191878	10.1126/science.aan4368	Unchecked	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
23398362	10.1042/bj20121418	Serine/threonine-protein kinase mTOR	4
23398362	10.1042/bj20121418	Tyrosine-protein kinase HCK	4
23398362	10.1042/bj20121418	Tyrosine-protein kinase Lck	4
23398362	10.1042/bj20121418	Protein kinase C beta type	4
16982756	10.1158/0008-5472.can-05-4290	LoVo	4
16982756	10.1158/0008-5472.can-05-4290	MDA-MB-231	4
23398362	10.1042/bj20121418	cGMP-dependent protein kinase 1	4
16982756	10.1158/0008-5472.can-05-4290	HUVEC	4
23398362	10.1042/bj20121418	Cyclin-dependent kinase 5/CDK5 activator 1	4
23398362	10.1042/bj20121418	Insulin receptor	4
23398362	10.1042/bj20121418	Insulin-like growth factor 1 receptor	4
16982756	10.1158/0008-5472.can-05-4290	Mitogen-activated protein kinase 1	3

Data from ChEMBL 36 via Core Engine