MLN8054是高效，选择性，有口服活性的极光激酶 (aur

MLN8054 is a potent, selective and orally available aurora A kinase inhibitor with an IC₅₀ of 4 nM.

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 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 Aautophosphorylation, and induce an increase in the Aurora B substrate, pHisH3^[2].

476.86

固体

C₂₅H₁₅ClF₂N₄O₂

869363-13-3

Room temperature in continental US; may vary elsewhere.

• [1]. Manfredi MG, et al. Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4106-11.  [Content Brief]

  [2]. Huck JJ, et al. MLN8054, an inhibitor of Aurora A kinase, induces senescence in human tumor cells both in vitro and in vivo. Mol Cancer Res. 2010 Mar;8(3):373-84.  [Content Brief]