Tivantinib, 1 mg

A staurosporine derivative supplied by STEMCELL Technologies as a laboratory chemical for research use. The substance is described as a crystalline solid and is identified by the synonym ARQ 197, with chemical 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 905854-02-6). The reported molecular formula is C23H19N3O2, the molecular weight is 369.4 g/mol, and the stated purity is ≥ 98%.

The compound acts as an HGF pathway inhibitor by binding to the inactive, dephosphorylated cRMET receptor tyrosine kinase in a manner that is not competitive with ATP. It is described as selective for cRMET, with a reported Ki ≅ 355 nM in a screen of 230 kinases. It also displays cytotoxic activity independent of its inhibition of cRMET and binds directly to the colchicine binding pocket of tubulin, reducing tubulin polymerization. Reported solubility values are ~0.1 mg/mL in a 1:5 solution of DMSO:PBS (pH 7.2), ~5 mg/mL in EtOH, and ~20 mg/mL in DMSO and DMF. According to the manufacturer, the product is stable at -20°C as supplied and remains stable for 12 months from the date of receipt when protected from prolonged exposure to light.

Published applications referenced by STEMCELL Technologies include induction of apoptosis in human myeloma CD138+ plasma cells in vitro and efficacy in a mouse xenograft model of myeloma, inhibition of metastatic growth of breast cancer cells in bone with reduced tumor-induced osteolysis in a mouse xenograft model, and perturbation of microtubule dynamics with G2/M arrest and apoptosis in a variety of cancer cell lines independently of cRMET inhibition. The safety data sheet classifies the substance as not a hazardous substance or mixture according to the Globally Harmonized System (GHS).