Tivantinib

Tivantinib
Clinical data
Other names	ARQ197; ARQ-197
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name (3R,4R)-3-(5,6-Dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-2,5-pyrrolidinedione;
CAS Number	905854-02-6;
PubChem CID	11494412;
ChemSpider	9669218;
UNII	PJ4H73IL17;
KEGG	D10173;
ChEMBL	ChEMBL2103882;
CompTox Dashboard (EPA)	DTXSID60920316 ;
ECHA InfoCard	100.231.891
Chemical and physical data
Formula	C23H19N3O2
Molar mass	369.424 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CC2=C3C(=CC=C2)C(=CN3C1)[C@H]4[C@@H](C(=O)NC4=O)C5=CNC6=CC=CC=C65;
	InChI 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; Key:UCEQXRCJXIVODC-PMACEKPBSA-N;

Tivantinib (ARQ197; by Arqule, Inc.) is an experimental small molecule anti-cancer drug. It is a bisindolylmaleimide that binds to the dephosphorylated MET kinase in vitro. (MET is a growth factor receptor.) Tivantinib is being tested clinically as a highly selective MET inhibitor.^[1] However, the mechanism of action of tivantinib is still unclear.^{[citation needed]}

Tivantinib displays cytotoxic activity via molecular mechanisms that are independent from its ability to bind MET, notably tubulin binding, which likely underlies tivantinib cytotoxicity.^[2]

Possible applications include non-small-cell lung carcinoma, hepatocellular carcinoma, and oesophageal cancer.^[3]

In 2017, it was announced that a phase III clinical trial for advanced hepatocellular carcinoma had failed to meet the primary endpoint.^[4]^[5]

References

^ "ArQule Announces Commencement of Phase 3 Clinical Trial with Tivantinib in Hepatocellular Carcinoma by Partner Kyowa Hakko Kirin in Japan". The Wall Street Journal. 4 February 2014. Archived from the original on 22 February 2014.
^ Basilico C, Pennacchietti S, Vigna E, Chiriaco C, Arena S, Bardelli A, et al. (May 2013). "Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET". Clinical Cancer Research. 19 (9): 2381–92. doi:10.1158/1078-0432.CCR-12-3459. PMID 23532890.
^ Spreitzer H (24 November 2014). "Neue Wirkstoffe – Tivantinib". Österreichische Apothekerzeitung (in German) (24/2014): 30.
^ "ArQule, Daiichi Sankyo Say Cancer Candidate Tivantinib Fails Phase III Trial". Genetic Engineering & Biotechnology News. February 2017.
^ "Tivantinib (ARQ 197)". ArQule. Archived from the original on 14 March 2017.

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[wsj-1] "ArQule Announces Commencement of Phase 3 Clinical Trial with Tivantinib in Hepatocellular Carcinoma by Partner Kyowa Hakko Kirin in Japan". The Wall Street Journal. 4 February 2014. Archived from the original on 22 February 2014.

[2] Basilico C, Pennacchietti S, Vigna E, Chiriaco C, Arena S, Bardelli A, et al. (May 2013). "Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET". Clinical Cancer Research. 19 (9): 2381–92. doi:10.1158/1078-0432.CCR-12-3459. PMID 23532890.

[Spreitzer-3] Spreitzer H (24 November 2014). "Neue Wirkstoffe – Tivantinib". Österreichische Apothekerzeitung (in German) (24/2014): 30.

[4] "ArQule, Daiichi Sankyo Say Cancer Candidate Tivantinib Fails Phase III Trial". Genetic Engineering & Biotechnology News. February 2017.

[5] "Tivantinib (ARQ 197)". ArQule. Archived from the original on 14 March 2017.

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See also

References