TIVANTINIB

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H19N3O2
Molecular Weight	369.4159
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1NC(=O)[C@H]([C@@H]1C2=CNC3=C2C=CC=C3)C4=CN5CCCC6=CC=CC4=C56

InChI

InChIKey=UCEQXRCJXIVODC-PMACEKPBSA-N

InChI=1S/C23H19N3O2/c27-22-19(16-11-24-18-9-2-1-7-14(16)18)20(23(28)25-22)17-12-26-10-4-6-13-5-3-8-15(17)21(13)26/h1-3,5,7-9,11-12,19-20,24H,4,6,10H2,(H,25,27,28)/t19-,20-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C23H19N3O2
Molecular Weight	369.4159
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.arqule.com/pipeline/tivantinib-arq-197/
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800023861 | https://www.ncbi.nlm.nih.gov/pubmed/20484018

Tivantinib (ARQ 197) is the first non-ATP-competitive small molecule that selectively targets the c-Met receptor tyrosine kinase. Exposure to Tivantinib resulted in the inhibition of proliferation of c-Met-expressing cancer cell lines as well as the induction of caspase-dependent apoptosis in cell lines with constitutive c-Met activity. ArQule and its collaborators Daiichi Sankyo and Kyowa Hakko Kirin are developing tivantinib as a potential therapy for many cancers. c-Met is overexpressed in many cancers. Tivantinib currently is in phase 3 clinical development for the treatment of hepatocellular carcinoma and non-small cell lung cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Hepatocyte growth factor receptor 56 Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20484018	Inhibitor 8504		355.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Non-small cell lung cancer 211 Sources: http://adisinsight.springer.com/drugs/800023861	Primary		Phase III 665	Unknown Approved Use Unknown
Hepatocellular carcinoma 83 Sources: http://adisinsight.springer.com/drugs/800023861	Primary		Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1459 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21976535	360 mg 2 times / day multiple, oral dose: 360 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TIVANTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2051 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21976535	120 mg 2 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TIVANTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
8257 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21976535	360 mg 2 times / day multiple, oral dose: 360 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TIVANTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13297 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21976535	120 mg 2 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TIVANTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/21976535	120 mg 2 times / day steady-state, oral dose: 120 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		TIVANTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY110860	https://www.001chemical.com/chem/search?q=DY110860
1PlusChem LLC	1P0037B8	https://www.1pchem.com/search?query=1P0037B8
AChemBlock	10396	http://www.achemblock.com/catalogsearch/result/?q=10396
AK Scientific	3211AH	https://aksci.com/item_detail.php?cat=3211AH
AK Scientific	SYN5688	https://aksci.com/item_detail.php?cat=SYN5688
Angene	AGN-PC-0WCRQJ	http://www.angenechemical.com/productshow/AGN-PC-0WCRQJ.html
Angene	AGN-PC-0WH9F3	http://www.angenechemical.com/productshow/AGN-PC-0WH9F3.html
AstaTech	73624	http://astatechinc.com/CPSResult.php?CRNO=73624
AstaTech	C77073	http://astatechinc.com/CPSResult.php?CRNO=C77073
Axon MedChem	1838	https://www.axonmedchem.com/product/1838
BioSynth	J-501255	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-501255
BLD Pharm	BD164231	http://www.bldpharm.com/search/Search.html?keyword=BD164231
BLD Pharm	BD224176	http://www.bldpharm.com/search/Search.html?keyword=BD224176
BOC Sciences	905854-02-6	http://www.bocsci.com/description.asp?cas=905854-02-6
Cayman Chemical	17135	http://www.caymanchem.com/app/template/Product.vm/catalog/17135
Chem Scene	CS-0030	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0030
Chem Scene	CS-M1129	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-M1129
Chem Scene	CS-M1640	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-M1640
ChemShuttle	101025	https://www.chemshuttle.com/catalogsearch/result/?q=101025
ChemShuttle	124902	https://www.chemshuttle.com/catalogsearch/result/?q=124902
Combi-Blocks	QK-3235	http://www.combi-blocks.com/cgi-bin/find.cgi?QK-3235
eMolecules	227979128	https://orderbb.emolecules.com/search/#?query=227979128
eMolecules	43338632	https://orderbb.emolecules.com/search/#?query=43338632
eMolecules	49262967	https://orderbb.emolecules.com/search/#?query=49262967
eMolecules	93724780	https://orderbb.emolecules.com/search/#?query=93724780
eNovation Chemicals	D372317	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D372317&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D770443	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D770443&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A2169	http://www.excenen.com/searchresultlist.php?id=EX-A2169
KeyOrganics	AS-16991	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16991
KeyOrganics	AS-74295	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74295
Lab Network	LN01301806	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01301806
Lab Network	LN01347522	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01347522
Lab Seeker	SC-86236	http://www.labseeker.com/search.php?keywords=SC-86236&category=0
LabSeeker	SC-86236	http://www.labseeker.com/search.php?keywords=SC-86236&category=0
Matrix Scientific	143758	http://www.matrixscientific.com/143758.html
Matrix Scientific	148391	http://www.matrixscientific.com/148391.html
mcule	MCULE-3523110909	https://mcule.com/MCULE-3523110909/
mcule	MCULE-6898207494	https://mcule.com/MCULE-6898207494/
mcule	MCULE-7825391847	https://mcule.com/MCULE-7825391847/
MedChem Express	HY-50686	https://www.medchemexpress.com/search.html?q=HY-50686&ft=&fa=&fp=
Molcore	MC110860	http://www.molcore.com/CatMC110860.html
Molnova	M16511	https://www.molnova.com/en/serch-list.html?keywords=M16511
MolPort	MolPort-021-805-013	https://www.molport.com/shop/molecule-link/MolPort-021-805-013
MolPort	MolPort-028-754-602	https://www.molport.com/shop/molecule-link/MolPort-028-754-602
MolPort	MolPort-046-860-428	https://www.molport.com/shop/molecule-link/MolPort-046-860-428
MuseChem	M015229	https://www.musechem.com/product/M015229.html
ShangHai Biochempartner	BCP000400	http://www.biochempartner.com/search_BCP000400
ShangHai Biochempartner	BCP02529	http://www.biochempartner.com/search_BCP02529
Synthonix	D65709	https://synthonix.com/catalogsearch/result/?q=D65709
Synthonix	D66049	https://synthonix.com/catalogsearch/result/?q=D66049
Toronto Research Chemicals	C955850	https://www.trc-canada.com/product-detail/?CatNum=C955850
Toronto Research Chemicals	T447200	https://www.trc-canada.com/product-detail/?CatNum=T447200
Vesino Industrial Co Ltd	VA12017	http://www.vsnchem.com/search.do?a=s&psize=20&q=VA12017

PubMed

Title	Date	PubMed
Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET--letter.	2013-08-01	23766362
Cytotoxic activity of tivantinib (ARQ 197) is not due solely to c-MET inhibition.	2013-05-15	23598276
Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer.	2011-08-20	21768463
Receptor kinase inhibitors target NSCLC: two antibodies and a small-molecule MET inhibitor.	2011-08-01	21815704
ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity.	2010-06	20484018
Invasive growth: a MET-driven genetic programme for cancer and stem cells.	2006-08	16862193
Met, metastasis, motility and more.	2003-12	14685170
Dysregulation of Met receptor tyrosine kinase activity in invasive tumors.	2002-04	11927612

Patents

Sample Use Guides

In Vivo Use Guide

The initially identified dose and schedule for clinical use (hepatocellular carcinoma treatment) was 360 mg twice daily. During study conduction, tivantinib dose was amended to 240 mg twice daily, due to a high incidence of neutropenia, without losing clinical efficacy.

Route of Administration: Oral

In Vitro Use Guide

Twelve human cancer cell lines representing various tumor types were treated with ARQ 197 at concentrations ranging from 0.03 to 30 μmol/L

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:30:49 GMT 2025` Edited by `admin` on `Mon Mar 31 18:30:49 GMT 2025`
Record UNII	PJ4H73IL17
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TIVANTINIB

Official Name

English

ARQ-197

Preferred Name

English

Tivantinib [WHO-DD]

Common Name

English

TIVANTINIB [JAN]

Common Name

English

tivantinib [INN]

Common Name

English

TIVANTINIB [MI]

Common Name

English

TIVANTINIB [USAN]

Common Name

English

(3R,4R)-3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)pyrrolidine-2,5-dione

Systematic Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/13/1202