Development and Therapeutic Potential of Small-Molecule Modulators of Circadian Systems

Author:

Chen Zheng1,Yoo Seung-Hee1,Takahashi Joseph S.2

Affiliation:

1. Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA;

2. Department of Neuroscience and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

Abstract

Circadian timekeeping systems drive oscillatory gene expression to regulate essential cellular and physiological processes. When the systems are perturbed, pathological consequences ensue and disease risks rise. A growing number of small-molecule modulators have been reported to target circadian systems. Such small molecules, identified via high-throughput screening or derivatized from known scaffolds, have shown promise as drug candidates to improve biological timing and physiological outputs in disease models. In this review, we first briefly describe the circadian system, including the core oscillator and the cellular networks. Research progress on clock-modulating small molecules is presented, focusing on development strategies and biological efficacies. We highlight the therapeutic potential of small molecules in clock-related pathologies, including jet lag and shiftwork; various chronic diseases, particularly metabolic disease; and aging. Emerging opportunities to identify and exploit clock modulators as novel therapeutic agents are discussed.

Publisher

Annual Reviews

Subject

Pharmacology,Toxicology

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