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

The CLKs (Cdc2-like kinases) belong to the dual-specificity protein kinase family and play crucial roles in regulating transcript splicing via the phosphorylation of SR proteins (SRSF1-12), catalyzing spliceosome molecular machinery, and modulating the activities or expression of non-splicing proteins. The dysregulation of these processes is linked with various diseases, including neurodegenerative diseases, Duchenne muscular dystrophy, inflammatory diseases, viral replication, and cancer. Thus, CLKs have been considered as potential therapeutic targets, and significant efforts have been exerted to discover potent CLKs inhibitors. In particular, clinical trials aiming to assess the activities of the small molecules Lorecivivint on knee Osteoarthritis patients, and Cirtuvivint and Silmitasertib in different advanced tumors have been investigated for therapeutic usage. In this review, we comprehensively documented the structure and biological functions of CLKs in various human diseases and summarized the significance of related inhibitors in therapeutics. Our discussion highlights the most recent CLKs research, paving the way for the clinical treatment of various human diseases.

 

Comments:

The CLKs, or Cdc2-like kinases, are members of the dual-specificity protein kinase family. They play vital roles in regulating transcript splicing by phosphorylating SR proteins (SRSF1-12), catalyzing the spliceosome molecular machinery, and modulating the activities or expression of non-splicing proteins. Dysregulation of these processes has been implicated in various diseases, including neurodegenerative diseases, Duchenne muscular dystrophy, inflammatory diseases, viral replication, and cancer. Consequently, CLKs have emerged as potential therapeutic targets, and considerable efforts have been made to discover potent CLK inhibitors.

Several small molecules have been investigated as potential inhibitors of CLKs in clinical trials. Lorecivivint has been studied in clinical trials to evaluate its activity in knee osteoarthritis patients. Similarly, Cirtuvivint and Silmitasertib have been investigated in different advanced tumor types for their therapeutic potential.

In this review, we provide a comprehensive documentation of the structure and biological functions of CLKs in various human diseases. We also summarize the significance of CLK inhibitors in therapeutic applications. By highlighting the most recent research on CLKs, this review aims to pave the way for the clinical treatment of various human diseases.

Overall, the review emphasizes the importance of understanding the role of CLKs in disease processes and the potential of CLK inhibitors as therapeutic agents. The advancements in this field hold promise for the development of novel treatment strategies for a wide range of diseases.

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