Chemical biology approaches to study and target circadian clocks and their components

Circadian rhythms are biological cycles of approximately 24 h that align physiology and behavior with the solar day, helping organisms coordinate their functions with the light/dark cycle. These rhythms are generated by molecular circadian clocks found in cells that are composed of transcription/translation negative feedback loops and regulate gene activity and protein production. The field of chemical biology has generated tools to track, modify, and manipulate clock proteins in living systems, providing a meaningful way to study these clocks and their components. Small molecules, covalent tags, and detectable reporters, among others, have been used to reveal how clocks keep time, respond to environmental signals, and differ across organisms. In this review, we highlight and describe chemical biology approaches used to study and modulate molecular circadian mechanisms that have expanded understanding of circadian protein dynamics and interactions in the contexts of mammalian and Drosophila models. The application of chemical biology strategies to study and target circadian clocks and their components can expand our fundamental knowledge via means that are otherwise inaccessible and point toward new strategies for treating clock-related disorders.