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

Development and Therapeutic Potential of Small-Molecule Modulators of Circadian Systems. Annu Rev Pharmacol Toxicol. 2017 Oct 02;: Authors: Chen Z, Yoo SH, Takahashi JS 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. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 58 is January 6, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates. ...
Source: Annual Review of Pharmacology and Toxicology - Category: Drugs & Pharmacology Authors: Tags: Annu Rev Pharmacol Toxicol Source Type: research