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Development and Therapeutic Potential of Small-Molecule Modulators of Circadian Systems
Annual Review of Pharmacology and Toxicology ( IF 12.5 ) Pub Date : 2018-01-08 00:00:00 , DOI: 10.1146/annurev-pharmtox-010617-052645
Zheng Chen 1 , Seung-Hee Yoo 1 , Joseph S. Takahashi 2
Affiliation  

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.

中文翻译:


昼夜系统小分子调节剂的开发及治疗潜力

昼夜节律系统驱动振荡基因表达来调节必需的细胞和生理过程。当系统受到干扰时,就会发生病理后果,并增加疾病风险。据报道,越来越多的小分子调节剂靶向昼夜节律系统。通过高通量筛选或从已知支架衍生而来的此类小分子已显示出有望成为改善疾病模型中生物时机和生理输出的候选药物。在这篇综述中,我们首先简要描述了昼夜节律系统,包括核心振荡器和蜂窝网络。介绍了时钟调节小分子的研究进展,重点是发展策略和生物功效。我们着重介绍了小分子在与时钟相关的病理学中的治疗潜力,包括时差和轮班;各种慢性疾病,特别是代谢性疾病;和老化。讨论了识别和利用时钟调节器作为新型治疗剂的新兴机会。

更新日期:2018-01-08
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