Network Version
Tivantinib Data Sheet
| Product Name: | Tivantinib |
 |
|---|---|---|
| CAS No.: | 905854-02-6 | |
| Cat. No.: | HY-50686 | |
| MWt: | 369.42 | |
| Formula: | C23H19N3O2 | |
| Purity : | >98% | |
| Solubility: | DMSO : 100 mg/mL (270.69 mM; Need ultrasonic) | |
| Mechanisms: | Target: Cancer | |
| Biological Activity: | ||
| Tivantinib is a highly selective c-Met tyrosine kinase inhibitor with a Ki of 355 nM. IC50 & Target:Ki: 355 nM (c-Met)[1] In Vitro: 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 Km of ATP is 50.5±2.2 μM, which is similar to the Km value of ATP. In these kinetic studies, Tivantinib inhibits human recombinant c-Met with a calculated inhibitory constant (Ki) 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 IC50 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]. In Vivo: Pharmacodynamically, the phosphorylation of c-Met in human colon xenograft tumors (HT29) is strongly inhibited by Tivantinib (ARQ 197), as assessed by a dramatic reduction of c-Met autophosphorylation 24 hours after a single oral dose of 200 mg/kg of Tivantinib. This same dosage in mice shows that tumor xenografts are exposed to sustained plasma levels of Tivantinib, consistent with the observed pharmacodynamic inhibition of c-Met phosphorylation and inhibition of proliferation of c-Met harboring cancer cell lines. A Cmax of 5.73 μg/mL (13 μM), an area under the concentration-time curve of 12.1 μg/mL h, and a t1/2 of 2.4 hours are measured. Plasma levels of Tivantinib 10 hours after dosing are determined to be 1.3 μM, >3-fold above the biochemical inhibitory constant of Tivantinib for c-Met[1]. | ||
1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA
Tel: 609-228-6898 Fax: 609-228-5909 Email: [email protected] Web:www.medchemexpress.com