CDK2 (Cyclin dependent Kinase 2) is an enzyme essential to the regulation of cell growth and division. Cyclin A2, an activator of CDK2, is often overexpressed in cancer cells, which is believed to promote carcinogenesis and is often associated with poor prognosis of cancer patients. Targeting CDK2 and other CDKs in cancer therapy has long been a focus for many researchers in both academia and industry, while no CDK inhibitor has been successfully tested in clinical trials to date. Therefore an effective Cyclin A2/CDK2 inhibitor with a new working mechanism would open up many new opportunities for cancer therapeutics development.
SDSU researchers have found and tested a lead compound which allosterically inhibits the activation of CDK2 by Cyclin A2. Upon binding, this compound changes the confirmation of CDK2, therefore inhibiting the enzymatic activity that is required in cell division. Experimental data has proved the allosteric nature of the binding. SDSU researchers are working on solving the structure of the compound-CDK2 complex and designing new compounds based on the structure of the lead compound to improve its efficacy. These compounds will become a new class of cancer therapeutic drugs and have a great commercialization potential.
This is a novel mechanism that regulates a well-known cancer related target molecule, which could lead to discovery of a new class of targeted cancer therapeutics. The allosteric regulation mechanism could provide greater selectivity and better modulatory control of the target. The lead compound has simple structure and was approved for human application, which would make the manufacturing cost low and the chance of FDA approval high.