| Description: |
TAK-901 is a non-selective Aurora kinase inhibitor (IC50s = 3.1, 10, and 4.2 nM for Aurora A, B, and C, respectively).It also inhibits JAK3, c-Src, CLK2, FGR, YES1, LRRK2, FLT3, Fyn, Abl, and FGFR2 (IC50s = 1.2-6.4 nM) and several other kinases. TAK-901 inhibits Aurora kinase complexes with IC50 values of 21 and 15 nM for the Aurora A and targeting protein for Xklp2 (TPX2) and Aurora B and inner centromere protein (INCENP) complexes, respectively. It decreases histone H3 phosphorylation in human prostate PC3 cancer cells (EC50 = 0.16 μM) and inhibits c-Src, FAK, FGFR2, FLT3, Abl, and Axl autophosphorylation in a panel of cancer cell lines (EC50s = 0.19-3.7 μM). TAK-901 inhibits the growth of lung, colon, stomach, skin, kidney, breast, ovarian, uterine, and prostate cancer cell lines (EC50s = 0.043-1.5 μM). In vivo, TAK-901 (40 mg/kg per day, i.v.) inhibits histone H3 phosphorylation and reduces tumor growth in an A2780 ovarian cancer nude rat xenograft model. TAK-901 also inhibits tumor growth in colorectal, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML) mouse xenograft models. |
