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ISSN: 2161-0444

Medicinal Chemistry
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Review Article

Pharmacological Modulators of Molecular Clock and their Therapeutic Potentials in Circadian Rhythm-Related Diseases

Gi Hoon Son1, Sooyoung Chung2, Victor D Ramirez3 and Kyungjin Kim4,5*

1Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, Korea

2Department of Brain and Cognitive Sciences, Scranton College, Ewha Womans University, Seoul, Korea

3Facultad de Ciencias Quimicas y Farmaceuticas, Universidad de Chile, Santiago, Chile/Emeritus Professor, Molecular Integrative Physiology, UIUC, USA

4Department of Brain and Cognitive Sciences, Daegu-Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea

5Korea Brain Research Institute (KBRI), Daegu, Korea

*Corresponding Author:
Kyungjin Kim
Department of Brain and Cognitive Sciences
Daegu-Gyeongbuk Institute of Science and Technology (DGIST)
Daegu 711-873, Korea
Tel: +82537856144
Fax: +82537856109
E-mail: [email protected]

Received date: December 12, 2016; Accepted date: December 20, 2016; Published date: December 24, 2016

Citation: Son GH, Chung S, Ramirez VD, Kim K (2016) Pharmacological Modulators of Molecular Clock and their Therapeutic Potentials in Circadian Rhythm-Related Diseases. Med Chem (Los Angeles) 6:724-733. doi: 10.4172/2161-0444.1000421

Copyright: © 2016 Son GH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Circadian rhythms regulate a wide range of biological processes and play a fundamental role in mammalian behavior, physiology, and metabolism. The hierarchically organized circadian timing system in mammals, with a master pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus and subsidiary oscillators in extra-SCN brain regions and peripheral tissues, mediates periodicities in physiological processes. It has been well recognized that disruption or misalignment of the intrinsic rhythms leads to diverse pathological states. Since mammalian circadian clock genes were first identified in the 1990’s, genetic and biochemical approaches have uncovered the molecular bases of the cell-autonomous and self-sustainable rhythms that are generated by two interlocking feedback loops of clock proteins. With our understanding of key features underlying the overt circadian rhythm and physiological outputs, it has emerged that pharmacological control of the circadian clock may provide a novel therapeutic strategy to treat a variety of circadian rhythm-related human diseases such as neuropsychiatric, metabolic, cardiovascular, and immune/inflammatory diseases, and even cancer. Pharmaceutical approaches to circadian clock may involve either development of drugs to treat such circadian-related disorders or combinational uses with existing therapeutic strategies to improve their therapeutic efficacy via the intrinsic clock-dependent mechanisms. In this review, we will focus on recent progress in discovery of small molecule chemical compounds that can pharmacologically modulate molecular circadian clock and their potential to be developed into therapeutic drugs.

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