Title:Cyclin-Dependent Kinase as a Novel Therapeutic Target: An Endless Story
Volume: 15
Issue: 2
Author(s): Ahmed Mohamed Etman, Sherif Sabry Abdel Mageed, Mohamed Ahmed Ali and Mahmoud Abd El Monem El Hassab*
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr city, Cairo, 11829,Egypt
Keywords:
CDK, cyclin, regulation, cell cycle, inhibitor, cancer.
Abstract: Cyclin-Dependent Kinases (CDKs) are a family of enzymes that, along with their Cyclin
partners, play a crucial role in cell cycle regulation at many biological functions such as proliferation,
differentiation, DNA repair, and apoptosis. Thus, they are tightly regulated by a number of inhibitory
and activating enzymes. Deregulation of these kinases’ activity either by amplification,
overexpression or mutation of CDKs or Cyclins leads to uncontrolled proliferation of cancer cells.
Hyperactivity of these kinases has been reported in a wide variety of human cancers. Hence, CDKs
have been established as one of the most attractive pharmacological targets in the development of
promising anticancer drugs. The elucidated structural features and the well-characterized molecular
mechanisms of CDKs have been the guide in designing inhibitors to these kinases. Yet, they remain
a challenging therapeutic class as they share conserved structure similarity in their active site.
Several inhibitors have been discovered from natural sources or identified through high throughput
screening and rational drug design approaches. Most of these inhibitors target the ATP binding
pocket, therefore, they suffer from a number of limitations. Here, a growing number of ATP noncompetitive
peptides and small molecules has been reported.
