[CAS NO. 905854-02-6]  Tivantinib

Tivantinib (ARQ 197) selectively inhibits c-Met activity in cell-free and cell-based assays. c-Met-expressing cancer cell lines treated with Tivantinib display either a dose-dependent loss of proliferative capacity or caspase-dependent apoptosis that positively correlates with either ligand-dependent c-Met activity or constitutively active c-Met. To examine the biochemical mode of inhibition of Tivantinib, kinetic analyses are done using recombinant human c-Met in a filtermat-based assay. The K _m of ATP is 50.5±2.2 μM, which is similar to the K _m value of ATP. In these kinetic studies, Tivantinib inhibits human recombinant c-Met with a calculated inhibitory constant (K _i ) of ~355 nM. In vitro exposure to Tivantinib inhibits constitutive c-Met phosphorylation in HT29 and MKN-45 cells, and HGF-induced c-Met phosphorylation in MDA-MB-231 and NCI-H441 cells with an IC ₅₀ of 100 to 300 nM ^[1] . Tivantinib is a low-molecular-weight compound, and is the first in class orally available selective inhibitor of c-Met ^[2] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.