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Recent Advances in the Development of Casein Kinase 1 Inhibitors
Sha-Sha Li1, Yue-Hui Dong2, Zhao-Peng Liu3
1Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Background:
The casein kinase 1 (CK1) family is involved in regulating many cellular processes, including membrane trafficking, DNA damage repair, cytoskeleton dynamics, cytoskeleton maintenance and apoptosis. CK1 isoforms, especially CK1δ and CK1ε have emerged as important therapeutic targets for severe disorders such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), familial advanced sleep phase syndrome and cancer. Due to the importance of CK1 for the pathogenesis of disorders, there are great interests in the development of CK1 inhibitors.
Methods:
Using SciFinder® as a tool, the publications about the biology of CK1 and the recent developments of CK1 inhibitors were surveyed with an exclusion of those published as patents.
Results:
This review presents the current state of knowledge on the development of CK1 inhibitors, including both synthetic small molecular inhibitors that were divided into 7 categories according to structural features, and the natural compounds. An overview of the advancement of CK1 inhibitors was given, with the introduction of various existing CK1 inhibitors, their inhibitory activities, and the structure-activity relationships.
Conclusion:
Through physicochemical characterization and biological investigations, it is possible to understand the structure-activity relationship of CK1 inhibitors, which will contribute to better design and discovery of potent and selective CK1 inhibitors as potential agents for severe disorders such as AD, ALS and cancer.
Insights
Casein kinase 1 (CK1) inhibitors are crucial for treating severe diseases like Alzheimer's and cancer. Understanding their structure-activity relationships aids in developing more potent and selective therapeutic agents.
Area of Science:
- Biochemistry
- Pharmacology
- Medicinal Chemistry
Background:
- Casein kinase 1 (CK1) family regulates vital cellular processes including DNA repair and apoptosis.
- CK1 isoforms (CK1δ, CK1ε) are key therapeutic targets for Alzheimer's disease (AD), ALS, and cancer.
- Developing CK1 inhibitors is of significant interest due to CK1's role in disease pathogenesis.
Purpose of the Study:
- To review the current advancements in the development of CK1 inhibitors.
- To categorize synthetic small molecule inhibitors and discuss natural compounds.
- To provide an overview of existing CK1 inhibitors, their activities, and structure-activity relationships.
Main Methods:
- A comprehensive literature survey was conducted using SciFinder®.
- Publications focused on CK1 biology and inhibitor development were reviewed.
- Patented research was excluded from the survey.
Main Results:
- The review categorizes synthetic small molecule CK1 inhibitors into seven structural groups.
- It details various existing CK1 inhibitors, their inhibitory potencies, and structure-activity relationships.
- Natural compounds with CK1 inhibitory potential are also discussed.
Conclusions:
- Understanding CK1 inhibitor structure-activity relationships is essential for drug design.
- Physicochemical characterization and biological studies are key to this understanding.
- This knowledge will facilitate the discovery of potent and selective CK1 inhibitors for treating severe disorders like AD, ALS, and cancer.
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