Tivantinib

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.

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 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

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.
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.

See also

• Template:Intracellular chemotherapeutic agents
• Template:Growth factor receptor modulators