Title:Exploration of Potential Cyclin-dependent Kinases and their Inhibitors to
Combat Abnormal Signalling and Cancer
Volume: 19
Issue: 2
Author(s): Pradeep Pilania, Sisir Nandi, Dinesh Kumar Meena and Brij K. Sharma*
Affiliation:
- Department of Chemistry, Government PG College, Bundi, 323001, Rajasthan, India
Keywords:
Cyclin-dependent kinases, mitotic cell cycle, abnormal signalling, cancer, potential inhibitors, proteolysis-targeting chimera.
Abstract: Regulation of cell proliferation depends on stimulatory and inhibitory factors that act
in a coordinated manner in response to external signals. Various agents, including mitogens,
growth factors, cytokines, and other external factors, can impact the mitotic cell cycle, resulting
in either provoking growth, differentiation, or apoptosis. Many kinases, such as protein kinases,
regulate mitotic cell proliferation through normal signalling. One of the major protein kinase
family members is cyclin-dependent kinases (CDK), which are responsible for the regulation of
cell cycle progression. If the cell cycle-regulatory mechanisms are permanently altered, it can
cause abnormal proliferation that leads to neoplasia. This can result in tumour development,
where the availability and expression of CDKs become altered, contributing significantly to impaired
cell proliferation. Changes like these are often a characteristic of cancer. CDK inhibitors
have shown significant clinical benefits in treating various types of tumours in recent years. The
output has been achieved by the clinical approvals of particular CDK inhibitors. Researchers
have also been studying the proteolysis-targeting chimera (PROTAC) molecule for the last two
decades. This molecule uses ubiquitin-mediated proteasome mechanisms to break down specific
targets, making it a promising method for targeted protein degradation (TPD). TPD has become
a promising therapeutic option for tackling disease-causing proteins that are otherwise challenging
to treat using traditional small molecules. This review provides an overview of the state of
knowledge and a general understanding of selective or nonselective CDK inhibitors and
PROTAC degraders currently under development or clinically approved congeners, focusing on
improving cancer therapy.
