Applications
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PHA680632 in association with radiation led to additive effects in cancer cells, especially in the p53-deficient cells. Combined ionising radiation (IR) and treatment of PHA680632 (100–400 nM) prior to IR led to an enhancement of radiation-induced Annexin V positive cells, micronuclei formation, and Brca1 foci formation only in HCT116 cells with deficient p53, other than the p53 wild-type counterparts. PHA-680632 showed potent anti-proliferative effects in a wide range of cell types with IC50 values of 0.06–7.15 μM, including HeLa, HCT116, HT29, LOVO, DU145, and NHDF cells. PHA-680632 (0.5 μM) caused polyploidy in tumor cells.
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Application
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HA-680632 (15–60 mg/kg) inhibited tumor growth in mice xenografts models of HL60, A2780, and HCT116 cells, by reducing tumor cell proliferation and increasing apoptosis. PHA-680632 (45 mg/kg) suppressed growth of activated ras-driven mammary tumors in mouse mammary tumor virus v-Ha-ras transgenic mice and results in complete tumor stabilization and partial regression.
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References:
[1]. Soncini, C., Carpinelli, P., Gianellini, L., Fancelli, D., Vianello, P., Rusconi, L., ... & Ceruti, R. (2006). PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clinical Cancer Research, 12(13), 4080-4089.
[2]. Tao, Y., Zhang, P., Frascogna, V., Lecluse, Y., Auperin, A., Bourhis, J., & Deutsch, E. (2007). Enhancement of radiation response by inhibition of Aurora-A kinase using siRNA or a selective Aurora kinase inhibitor PHA680632 in p53-deficient cancer cells. British Journal of Cancer, 97(12), 1664.
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