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
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.