MLN8054

MLN8054 is a potent, selective and orally available aurora A kinase inhibitor with an IC₅₀ of 4 nM. IC50 & Target: IC50: 4 nM (Aurora A), 172 nM (Aurora B)^[1] In Vitro: MLN8054 is an ATP-competitive, reversible inhibitor of recombinant Aurora A kinase. MLN8054 is >40-fold more selective for Aurora A compared with the family member Aurora B. MLN8054 selectively inhibits Aurora A over Aurora B in cultured human tumor cells. MLN8054 treatment results in G2/M accumulation and spindle defects and inhibits proliferation in multiple cultured human tumor cells lines. MLN8054 effectively inhibits the growth of cells from diverse tissue origins with IC₅₀ values ranging from 0.11 to 1.43 μM^[1]. Treatment of human tumor cells grown in culture with MLN8054 shows a number of morphologic and biochemical changes associated with senescence^[2]. In Vivo: In the HCT-116 tumor-bearing mice, MLN8054 treatment inhibits tumor growth dose dependently. MLN8054 is generally well tolerated. MLN8054 also inhibits the growth of the PC-3 tumor xenograft in nude mice. MLN8054 Treatment Results in Inhibition of Aurora A, Accumulation of Mitotic Cells, and Apoptosis in vivo^[1]. MLN8054 selectively inhibits Aurora A kinase activity when dosed at 30 mg/kg. At this dose in HCT116 tumor tissue, MLN8054 has been shown to inhibit Aurora A autophosphorylation, and induce an increase in the Aurora B substrate, pHisH3^[2].