Identification and development of clock-modulating small molecules – an emerging approach to fine-tune the disrupted circadian clocks

ABSTRACT

Circadian timing system (CTS) enables living organisms to maintain circadian coherence in physiology, metabolism, and behavior. Mammalian CTS comprises central clock; the suprachaismatic nuclei in the brain and peripheral clocks scattered throughout the body. All clocks have similar cell-autonomous oscillator comprises a set of circadian genes that confer the living forms with capacity to generate persistent circadian rhythms. Emerging studies convincingly demonstrate that proper functioning of the CTS is vital for all living forms. Dysregulation of CTS leads to multitude of pathologies, naming the few, such as metabolic, immune, and sleep disorders, neurodegenerative and cardiovascular diseases, and cancer. Therefore, there is a growing interest to exploit circadian clocks as a therapeutic target. Efforts are made to identify the small molecules with potential to modulate the functional state of disrupted circadian clock. Many clock-modulating small molecules have been identified and their therapeutic role has been exploited in several diseases. However, the area of research is still in formative years. Current review presents the strategies that can be deployed for identification and development of clock-modulating small molecules. Moreover, this review also presents an emerged data on clock-modulating small molecules that have shown potential to modulate the circadian clocks.

Abbreviations: CRY: cryptochrome; PER: period; CK: casein kinase; AMPK: 5ʹAMP-activated protein kinase; SIRT1: sirtuin 1.

KEYWORDS:

• Circadian clock
• circadian timing system
• clock-modulating small molecules
• peripheral clocks
• suprachaismatic nuclei
• therapeutic drugs

Acknowledgments

Prof. Atanu Kumar Pati and Prof. Arti Parganiha, School of Studies in Life Sciences, Pt. Ravishankar Shukla University, Raipur, India are highly acknowledged for providing an opportunity to work with them and providing possible support and lab facility to carry out the research. University Grants Commission, New Delhi, India, is also highly acknowledged for providing me fellowship through DRS-SAP scheme sanctioned in the thrust area - Chronobiology to the School of Studies in Life Sciences, Pt. Ravishankar Shukla University, Raipur, India.

Disclosure statement

No potential conflict of interest was reported by the author.