Development of a specific CDC2 inhibitor peptide derived from cyclin B1 and analysis of cytotoxic effects of novel 1,2,4-oxadiazole compounds
Cell cycle kinases are increasingly becoming important therapeutic targets for cancer research due to their importance in cellular signaling. In this study we report the development of a specific cell division cycle 2 (CDC2) kinase inhibitor, derived from the CDC2 activator cyclin B1. The inhibitor was found to be selective for both CDC2 and CDK2 kinases. Further study showed that binding of the identified inhibitor for CDK2 was stronger than the binding of the CDK2 activator full length cyclin B1. In the second project, we report the cytotoxic effects of novel 1,2,4-oxadiazole compounds that were synthesized by our collaborator Dr. Dalip Kumar of the Birla Institute of Technology of Science, India. Fourteen novel 1,2,4-oxadiazole compounds were used to treat various human prostate cancer (PC3, DU145, LnCap), breast cancer (MCF7, MDA-MB-231), and pancreatic cancer (PaCa2) cell lines. The IC50 values of the 1,2,4-oxadiazole compounds were determined and used to identify potential anticancer drugs and to identify the structure-activity relationships of these compounds.
Shah, Purdue University.
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