Baowen Qi, L. Zhong, Jun He
Aug 5, 2019
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Influential Citations
8
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Quality indicators
Journal
Journal of medicinal chemistry
Abstract
Aurora and Polo-like kinases control the G2/M phase in cell mitosis, which are both considered as crucial targets for cancer cell proliferations. Here, naphthalene-based Aurora/PLK co-inhibitor as leading compound were designed through in silico approach and a total of 36 derivatives were synthesized. One candidate (AAPK-25) was selected under in vitro cell based high throughput screening with an IC50 value=0.4 μM to human colon cancer cell HCT-116. A kinome scan assay showed that AAPK-25 was remarkably selective to both Aurora and PLK families. The relevant genome pathways were also depicted by microarray based gene expression analysis. Furthermore, validated from a set of in vitro and in vivo studies, AAPK-25 significantly inhibited the development of the colon cancer growth and prolonged the median survival time at the end of the administration (p<0.05). To sum up, AAPK-25 has a great potential to be developed for a chemotherapeutic agent in clinical use.