Discovery For Anticancer Compounds Targeting To CDK1

CDK (Cyclin-dependent kinase) inhibitors are potential candidates for anti-cancer. CDK1 as a serine/threnoine protein kinase is activated at G2/M points in the cell cycle. It is critical for progression throughout the cell cycle. In addition, CDK1 is fundamental for cell division in all eukaryotes studied so far, since its inactivation prevents mitosis. Therefore, it is a useful approach for anticancer drug discovery to screen CDK1 inhibitors.In order to find the CDK1 inhibitors from the small molecular compounds and the Chinese traditional medicine herbs, we established a high-throughput screening (HTS) platform, a DELFIA (Dissociation -Enhancement Lanthanide FluoroImmunoAssay) assay, for screening anticancer compounds targeting to CDK1. We utilized a CDK1 Protein Kinase Assay System to screen CDK1 inhibitors from a natural component library derived from the traditional Chinese medicine herbs.So far, we screened 240 small molecular compounds with potential inhibitory activity for CDK1. Our results indicated that 6 compounds and LA had the inhibitory activity for CDK1 as compared with the control. In addition, we screened natural components derived from the traditional Chinese medicine herbs with anticancer effects. Five components with inhibitory activity for CDK1 were found in the natural component library. To validate the anti-cancer effects, we treated HCC cell line SMMC-7721, leukemia cell line U937, Jurkat, and breast cancer cell line MCF-7/MIT with the compounds. Cell morphology was observed by microscope. The inhibition of cell growth was measured by MTT and Trypan blue exclution test. Furthermore, Cell cycle, apoptosis, and drug resistance were analyzed by flow cytometry. Based on these results, we confirm the anticancer ability of these compounds.