Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases

Area of Science:

• Molecular Biology
• Biochemistry
• Pharmacology

Background:

• Cdc2-like kinases (CLKs) are dual-specificity protein kinases vital for regulating transcript splicing through SR protein phosphorylation.
• Dysregulation of CLKs is associated with numerous diseases, including neurodegenerative disorders, Duchenne muscular dystrophy, inflammatory conditions, viral infections, and various cancers.
• CLKs' critical roles in cellular processes and disease pathogenesis position them as significant therapeutic targets.

Purpose of the Study:

• To comprehensively review the structure and biological functions of CLKs in human diseases.
• To summarize the therapeutic potential of CLK inhibitors.
• To highlight recent advancements in CLK research for clinical applications.

Main Methods:

• Literature review of CLK structure, function, and disease association.
• Analysis of CLK inhibitor development and clinical trial data.
• Synthesis of current research trends in CLK-targeted therapeutics.

Main Results:

• CLKs play multifaceted roles in gene expression regulation, including splicing modulation.
• Aberrant CLK activity is a common hallmark in diverse pathological conditions.
• Several small molecule CLK inhibitors, such as Lorecivivint, Cirtuvivint, and Silmitasertib, are under clinical investigation.

Conclusions:

• CLKs are crucial regulators of cellular processes and are implicated in a wide spectrum of human diseases.
• Targeting CLKs with specific inhibitors represents a promising therapeutic strategy.
• Continued research into CLKs and their inhibitors holds significant potential for developing novel treatments for various diseases.