Three Aurora kinases, A-C, are involved in phosphorylation events that are critical for the completion of mitosis. Aurora A, involved in centrosomal assembly and acentrosomal spindle assembly, is overexpressed in many tumors. Phthalazinone pyrazole is a potent inhibitor of Aurora A kinase (IC50 = 31 nM). It does not inhibit Aurora B kinase at doses up to 100 μM. Phthalazinone pyrazole inhibits the proliferation of HCT116, COLO 205, and MCF-7 cells (IC50 = 7.8, 2.9, and 1.6 μM, respectively).
Phthalazinone pyrazole is a potent, selective, and orally active inhibitor of Aurora-A kinase with an IC50 of 0.031 μM. Phthalazinone pyrazole can arrests mitosis and subsequently inhibit tumor growth via apoptosis of proliferating cells. Phthalazinone pyrazole suppresses the epithelial-mesenchymal transition (EMT) during the differentiation of hepatocyte-like cells (HLCs) from human embryonic stem cells[1][2].
phthalazinone pyrazole potently inhibited the activity of aurora a kinase with an ic50 of 31 nm. it showed no inhibitory effect on aurora b kinase at doses up to 100 μm. phthalazinone pyrazole inhibited the proliferation of hct116, colo205, and mcf-7 cells with ic50 values of 7.8, 2.9, and 1.6 μm, respectively [1].
Aurora-A: 0.031 μM (IC50)
[1] prime m e, courtney s m, brookfield f a, et al. phthalazinone pyrazoles as potent, selective, and orally bioavailable inhibitors of aurora-a kinase[j]. journal of medicinal chemistry, 2010, 54(1): 312-319.
[2] vader g, lens s m a. the aurora kinase family in cell division and cancer[j]. biochimica et biophysica acta (bba)-reviews on cancer, 2008, 1786(1): 60-72.
