Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases.
Mengqiu SongLuping PangMengmeng ZhangYingzi QuKyle Vaughn LasterZigang DongPublished in: Signal transduction and targeted therapy (2023)
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.
Keyphrases
- knee osteoarthritis
- duchenne muscular dystrophy
- endothelial cells
- clinical trial
- protein kinase
- end stage renal disease
- poor prognosis
- ejection fraction
- induced pluripotent stem cells
- chronic kidney disease
- small molecule
- oxidative stress
- randomized controlled trial
- newly diagnosed
- sars cov
- risk assessment
- squamous cell carcinoma
- papillary thyroid
- long non coding rna
- young adults
- squamous cell
- patient reported outcomes
- replacement therapy
- phase iii
- atomic force microscopy