tcsc0243 TAK-901

TAK-901 is a multi-targeted aurora inhibitor with IC₅₀s of 21 and 15 nM for aurora A and B, respectively.

IC50 & Target: IC50: 21 nM (aurora A), 15 nM (aurora B), 1.2 nM (JAK3), 1.3 nM (Src), 2 nM (FGR), 5 nM (FLT3)^[1]

In Vitro: TAK-901 exhibits time-dependent, tight-binding inhibition of Aurora B, but not Aurora A. Consistent with Aurora B inhibition, TAK-901 suppresses cellular histone H3 phosphorylation and induces polyploidy. In various human cancer cell lines, TAK-901inhibits cell proliferation with effective concentration values from 40 to 500 nM. Examination of a broad panel of kinases in biochemical assays reveals inhibition of multiple kinases. However, TAK-901 potently inhibits only a few kinases other than Aurora B in intact cells, including FLT3 and FGFR2^[1].

In Vivo: In rodent xenografts, TAK-901 exhibits potent activity against multiple human solid tumor types, and complete regression is observed in the ovarian cancer A2780 model. TAK-901 also displayed potent activity against several leukemia models. TAK-901 induces pharmacodynamic responses consistent with Aurora B inhibition and correlating with retention of TAK-901 in tumor tissue^[1].