c-Kit-IN-3

2363169-01-9

516.90

H2O : < 0.1 mg/mL (insoluble); DMSO : >= 100 mg/mL (193.46 mM)

Protein Tyrosine Kinase/RTK

c-Kit-IN-3 (Compound 18) is a potent and selective c-KIT kinase inhibitor with an IC₅₀s of 4 nM, 8 nM for c-KIT wt and c-KIT T670I, respectively. c-Kit-IN-3 displays great potencies against most of the gain-offunction mutations in the juxtamembrane domain, drugresistant mutations in the ATP binding pocket, and activation loops^[1]. IC50 & Target: IC50: 4 nM (c-KIT w) and 8 nM (c-KIT T670I)^[1] In Vitro: c-Kit-IN-3 (Compound 18; 0.1-10 uM; 6 days; primary GIST patient cells) exhibits dose-dependent antiproliferative effects^[1].
c-Kit-IN-3 (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 (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 (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 potently inhibits the activity of CSF1R (IC₅₀: 18 nM), PDGFRalpha (IC₅₀: 25 nM), RET (IC₅₀: 34 nM), and it relatively less potently inhibits DDR1 (IC₅₀: 135 nM), FLT4 (IC₅₀: 121 nM), and PDGFRbeta (IC₅₀: 97 nM)^[1].
c-Kit-IN-3 (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]. In Vivo: c-Kit-IN-3 (Compound 18; oral gavage; 20-100 mg/kg/day; for 11 days; female BALB/C-nu mice) treatment dose dependently inhibits the tumor progression^[1].
c-Kit-IN-3 (1 mg/kg (iv for mice, rats, dog); 10 mg/kg (p.o. for mice, rats ) and 5 mg/kg (p.o. for dog)) has T_1/2 of 4.5 h, 6.4 h, 19.4 h for mice, rats and dogs, respectively. And it possesses acceptable bioavailability in mice (F = 43%), rats (F = 50%), and dogs (F = 81%)^[1].