c-Kit-IN-3 (hydrochloride)

553.36

10 mM in DMSO

Protein Tyrosine Kinase/RTK

c-Kit-IN-3 hydrochloride (Compound 18) is a potent c-KIT kinase inhibitor, which is potent and selective against BaF3-tel-c-KIT (IC₅₀ of 4 nM) and a broad spectrum of drug-resistant mutants (IC₅₀ of 8 nM for BaF3-tel-c-KIT-T670I) with improved bioavailability^[1]. IC50 & Target: IC50: 4 nM (BaF3-tel-c-KIT); 8 nM (BaF3-tel-c-KIT-T670I)^[1] In Vitro: c-Kit-IN-3 hydrochloride (Compound 18; 0.006 uM-1.37 uM) potently inhibits the growth of c-KIT-dependent GIST cancer cells, such as GIST-T1 (IC50: 0.006 uM); GIST-882 (IC50: 0.013 uM); GIST-T1-T670I (IC50 : 0.011 uM); GIST-5R (IC50: 0.073 uM); GIST-48B (IC50: 1.37 uM), respectively^[1].
c-Kit-IN-3 hydrochloride(Compound 18; 0.01-1 uM; 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)^[1].
c-Kit-IN-3 hydrochloride (Compound 18; 0.01-1 uM; 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^[1].
c-Kit-IN-3 hydrochloride (Compound 18; 0.1-10 uM; 6 days; primary GIST patient cells) exhibits dose-dependent antiproliferative effects^[1].
c-Kit-IN-3 hydrochloride (Compound 18; 0-1 uM; 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)^[1].
c-Kit-IN-3 hydrochloride (Compound 18; 0-1 uM; 2 hours) induces dose-dependent cell apoptotic death (by examining the cleaved PARP and cleaved caspase 3) and arrest the cell cycle into the G0/G1 phase in all of these three cell lines^[1].
In Vivo: c-Kit-IN-3 hydrochloride (Compound 18; 40-100 mg/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 100 mg/kg/day. And do not affect the animal weights^[1].