CCT241736

CCT241736 is a potent and orally bioavailable dual FLT3 and Aurora kinase inhibitor, which inhibits Aurora kinases (Aurora-A K_d, 7.5 nM, IC₅₀, 38 nM; Aurora-B K_d, 48 nM), FLT3 kinase (K_d, 6.2 nM), and FLT3 mutants including FLT3-ITD (K_d, 38 nM) and FLT3(D835Y) (K_d, 14 nM). IC50 & Target: IC50: 38 nM (Aurora-A)^[1]
Kd: 7.5 nM (Aurora-A), 48 nM (Aurora-B), 6.2 nM (FLT3), 38 nM (FLT3-ITD), 14 nM (FLT3(D835Y))^[1] In Vitro: CCT241736 (Compound 27e) is a potent and orally bioavailable dual FLT3 and Aurora kinase inhibitor, which inhibits Aurora kinases (Aurora-A K_d, 7.5 nM, IC₅₀, 38 nM, Aurora-B K_d, 48 nM), FLT3 kinase (K_d, 6.2 nM), and FLT3 mutants including FLT3-ITD (K_d, 38 nM) and FLT3(D835Y) (K_d, 14 nM). CCT241736 exhibits antiproliferative activity in a range of human tumor cell lines, such as HCT116 human colon carcinoma (GI₅₀, 0.300 μM), the human FLT3-ITD positive AML cell lines MOLM-13 (GI₅₀, 0.104 μM) and MV4-11 (GI₅₀, 0.291 μM). CCT241736 also inhibits both the autophosphorylation of Aurora-A at T288 (a biomarker for Aurora-A inhibition: IC₅₀, 0.030 μM) and histone H3 phosphorylation at S10 (a biomarker for Aurora-B inhibition: IC₅₀, 0.148 μM), consistent with potent cellular activity versus both Aurora-A and -B. CCT241736 suppresses Aurora-A in MOLM-13 cells with concomitant inhibition of FLT3 signaling^[1]. In Vivo: CCT241736 (50, 100 mg/kg, b.i.d, p.o.) dose-dependently suppresses the growth of MV4-11 human tumor xenografts, and completely abolishes the tumors at 100 mg/kg via p.o. administration twice a day^[1].