General description

A cell-permeable quinoline compound that acts as a potent inhibitor against the kinase activities of HGF (Cat. No. 375228) receptor c-Met and MSP (Macrophage Stimulating Protein) receptor RON (IC₅₀ = 4 and 9 nM, respectively), while exhibiting much weaker potency toward Lck, Tie2, Src, BTK, IGFR, or VEGFR2 (IC₅₀ = 160, 400, 410, 710, 1000, and 1900 nM, respectively), and little or no activity against B-Raf and more than 20 other kinases IC₅₀ >1 µM). Shown to effectively supress (IC₅₀﹤100 nM) the ligand-induced autophosphorylations of wild-type c-Met (in HT-29 and BxPC3 cultures) and RON (in NIH3T3 RON and BxPC3 cultures) as well as the ligand-independent autophosphorylations of the constitutively active mutants TPR-Met and RONδ160 (in NIH3T3 TRP-Met and HT-29 cultures, respectively). Reported to inhibit NIH3T3 TRP-Met and U-87 tumor growth in mice in vivo in a dose-dependent manner (complete inhibition via daily p.o. dose of 100 mg/kg), but is less efficacious against HT-29, whose in vivo tumor growth is also dependent on V600E B-raf.

A cell-permeable quinoline compound that acts as a potent inhibitor against the kinase activities of HGF receptor c-Met and MSP (Macrophage Stimulating Protein) receptor RON (IC₅₀ = 4 and 9 nM, respectively), while exhibiting much weaker potency toward Lck, Tie2, Src, BTK, IGFR, or VEGFR2 (IC₅₀ = 160, 400, 410, 710, 1000, and 1900 nM, respectively), and little or no activity against B-Raf and more than 20 other kinases IC₅₀ >1 M). Shown to effectively supress (IC₅₀﹤100 nM) the ligand-induced autophosphorylations of wild-type c-Met (in HT-29 and BxPC3 cultures) and RON (in NIH3T3 RON and BxPC3 cultures) as well as the ligand-independent autophosphorylations of the constitutively active mutants TPR-Met and RONδ160 (in NIH3T3 TRP-Met and HT-29 cultures, respectively). Reported to inhibit NIH3T3 TRP-Met and U-87 tumor growth in mice in vivo in a dose-dependent manner (complete inhibition via daily p.o. dose of 100 mg/kg), but is less efficacious against HT-29, whose in vivo tumor growth is also dependent on V600E B-raf.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Zhang, Y., et al. 2008. Cancer Res.68, 6680.

Packaging

Packaged under inert gas

5 mg in Plastic ampoule

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Warning

Toxicity: Standard Handling (A)