Tivantinib (ARQ197; by Arqule, Inc.) is an experimental small molecule anti-cancer drug. It is a

bisindolylmaleimide Bisindolylmaleimide is an organic compound that forms the core chemical structure of a variety of biologically active compounds. This core structure includes a central maleimide group with two indole groups attached. Examples of bisindolylmalei ...

that binds to the dephosphorylated

MET kinase c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is encoded by the ''MET'' gene. The protein possesses tyrosine kinase activity. The primary single chain precursor protein is ...

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

''. (MET is a

growth factor receptor A growth factor receptor is a receptor that binds to a growth factor. Growth factor receptors are the first stop in cells where the signaling cascade for cell differentiation and proliferation begins. Growth factors, which are ligands that bind to ...

.) Tivantinib is being tested clinically as a highly selective

MET inhibitor c-Met inhibitors are a class of small molecules that inhibit the enzymatic activity of the c-Met tyrosine kinase, the receptor of hepatocyte growth factor/scatter factor (HGF/SF). These inhibitors may have therapeutic application in the treatment ...

. However, the mechanism of action of tivantinib is still unclear. Tivantinib displays cytotoxic activity via molecular mechanisms that are independent from its ability to bind MET, notably tubulin binding, which likely underlies tivantinib cytotoxicity. Possible applications include

non-small-cell lung carcinoma Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to s ...

, hepatocellular carcinoma, and

oesophageal cancer Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voi ...

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

References

See also