Sha-Sha Li, Yue-Hui Dong and Zhao-Peng Liu* Pages 1585 - 1604 ( 20 )
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.
Casein kinase 1 (CK1), inhibitor, chemical, small molecules, anticancer agents, drug design.
Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Jinan Vocational College of Nursing, Jinan 250102, Department of Medicinal Chemistry, Key laboratory of Chemical Biology (Ministry of Education), School of pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012