Small Molecules Modulating Mammalian Biological Clocks: Exciting New Opportunities for Synthetic Chemistry

doi:10.1016/j.chempr.2020.08.011

Chem

Volume 6, Issue 9, 10 September 2020, Pages 2186-2198

https://doi.org/10.1016/j.chempr.2020.08.011 Get rights and content

Under an Elsevier user license

open archive

The Bigger Picture

Challenges and opportunities:

•
Increasing opportunities for the discovery of new circadian clock modulators, which are attractive drug candidates for clock-related diseases in pharmaceutical industry, and to enhance crop yield in agriculture.
•
Development of new reactions for rapid access to hit compound derivatives, accelerating structure-activity relationship studies, which are generally time consuming.
•
New approaches for target identification of clock-modulating small molecules, which is still challenging, enable molecular-level understanding and new structural designs.

Summary

The circadian clock is an intrinsic time-keeping system that controls daily rhythms in almost all living organisms on the earth. Daily rhythms are observed in various life phenomena, such as sleep-wake cycles, body temperature, blood pressure, and hormone secretion in animals, and stomatal movements and photosynthetic activity in plants. Therefore, controlling the circadian clock in a precise manner will make significant contributions in the elucidation of their molecular mechanisms, as well as to medicine and agriculture. Genetic and molecular biological studies have made substantial progress in understanding of molecular clock mechanisms. For further investigation of the basic mechanisms as well as for therapeutic applications, small-molecule compounds will provide unique opportunities. In this perspective, we highlight chemical biology approaches toward mammalian circadian clock modulation by using small synthetic molecules.

Graphical Abstract

UN Sustainable Development Goals

SDG3: Good health and well-being

Keywords

circadian clock

small molecules

synthetic chemistry

chronobiology