CCT241736 (Mobinitinib) is a potent, orally bioavailable dual FLT3/Aurora kinase inhibitor with binding Kd of 7.5/48/6.2/38/14 nM for Aurora-A/Aurora-B/FLT3 WT/FLT3-ITD/FLT3(D835Y) respectively.
CCT241736 (Mobinitinib) shows S(10) selectivity score of 0.057 in a 442-kinase panel (containing 386 nonmutant kinases) at a concentration of 1 μM using the KINOMEScan technology.
CCT241736 (Mobinitinib) displays antiproliferative activity in a range of human tumor cell lines, including HCT116 human colon carcinoma (GI50 = 0.300 μM) and the human FLT3-ITD positive AML cell lines MOLM-13 (GI50 = 0.104 μM) and MV4–11 (GI50 = 0.291 μM). inhibited 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) in HeLa cells.
CCT241736 (Mobinitinib) (50-100 mg/kg po b.i.d.) significantly inhibits the growth of MV4–11 human FLT3-ITD positive AML tumor xenografts in athymic mice.