We continue our series in the Biologics campaign – this time it is about the Cyclin-Dependent Kinases (CDKs).
The CDKs are serine/threonine kinases whose enzymatic activity is regulated by interactions with definite subunits - cyclins and CDK inhibitors (CKIs). CDKs play essential roles in cell proliferation by regulating cell-cycle checkpoints and transcriptional events in response to several extra- and intracellular cues. Hence the dysregulation of CDKs could be a hallmark of cancers, and inhibition of specific CDKs is considered an attractive target in cancer treatment.
You can find more about the role of CDKs in various cancer progression here.
The prospect of inhibition of cell division has made the CDKs a long-standing target in cancer therapy. But for now, there are numerous pan-selective inhibitors in clinical trials. In this paper, authors describe the discovery of a series of especially selective CDK2 inhibitors based on dihydro‑6H‑pyrrolo[2,3‑d]pyrimidin-6-one scaffold. The design and development from the initial hit led to compounds that possess promising initial general kinome selectivity and minimal CYP/hERG inhibition. Further investigations represent such compounds as valuable tools to study the effects of CDK2-selective inhibition in in vivo models.
More information about this research is here.
