Small-Molecule Kinase Inhibitors Modulating Circadian Rhythms

The circadian clock mechanism generates 24-h rhythms crucial for regulating various physiological processes, and its dysregulation has been implicated in numerous diseases. In cells, the circadian clock operates through a transcriptional-translational feedback loop, where phosphorylation plays a pivotal role in maintaining accurate circadian rhythms. Consequently, kinase inhibitors have emerged as promising targets for modulating the circadian clock and potentially treating circadian-related diseases. This review aims to provide an overview of the current state-of-the-art of kinase inhibitors with effects on the mammalian circadian clock. By highlighting promising targets and addressing the limitations of existing inhibitors, this review intends to provide a guide for future research efforts towards the development of novel compounds for the treatment of circadian-related disorders. Furthermore, it highlights the critical discrepancy between in vitro activity and in vivo effectiveness, emphasizing the critical need for rigorous in vivo validation to translate the therapeutic potential of kinase inhibitors into effective treatments for these disorders.