| 应用 |
c-Kit-IN-3 (Compound 18) is a potent and selective c-KIT kinase inhibitor with an IC50 of 4 nM. c-Kit-IN-3 displays great potencies against c-KIT kinase and a broad spectrum of drug-resistant mutants in the biochemical assay. c-Kit-IN-3 has improved bioavailability.
c-Kit-IN-3 (Compound 18; 0.1-10 μM; 6 days; primary GIST patient cells) exhibits dose-dependent antiproliferative effects.c-Kit-IN-3 (Compound 18; 0.01-1 μM; 24 hours; GIST-T1, GIST-T1-T670I, and GIST-5R cells) treatment induces dose-dependent cell apoptotic death (by examining the cleaved PARP and cleaved caspase 3).c-Kit-IN-3 (Compound 18; 0.01-1 μM; 24 hours; GIST-T1, GIST-T1-T670I, and GIST-5R cells) treatment arrests the cell cycle into the G0/G1 phase in all of these three cell lines.c-Kit-IN-3 (Compound 18; 0-1 μM; 24 hours) blocks the autophosphorylation of c-KIT pY703, pY719, and pY823 in GIST-T1, GIST-T1-T670I, and GIST-5R, respectively, cells at a concentration of 30 nM and inhibits the downstream signaling mediators pAKT (T308/S473), pS6 (S235/236), and pERK (T202/204). c-Kit-IN-3 (Compound 18; 0.006 μM-1.37 μM) potently inhibits the growth of c-KIT-dependent GIST cancer cells, such as GIST-T1 (IC50: 0.006 μM); GIST-882 (IC50: 0.013 μM); GIST-T1-T670I (IC50: 0.011 μM); GIST-5R (IC50: 0.073 μM); GIST-48B (IC50: 1.37 μM), respectively. Cell Proliferation Assay Cell Line: Primary GIST patient cells
c-Kit-IN-3 (Compound 18; 40-100mg/kg; oral gavage; daily; for 11 days; for 4 weeks; female BALB/C-nu mice) treatment dose dependently inhibits the BaF3-tel-c-KIT-T670I tumor progression and exhibited almost 100% TGI (tumor growth inhibition) at a dosage of 100mg/kg/day. And do not affect the animal weights. Animal Model: Female BALB/C-nu mice bearing established BaF3-tel-c-KIT-T670I tumor xenografts |
