Development and Therapeutic Potential of Small-Molecule Modulators of Circadian Systems.
Development and Therapeutic Potential of Small-Molecule Modulators of Circadian Systems.
复制标题
DOI：
10.1146/annurev-pharmtox-010617-052645
复制
发表时间：
2018-01-06
影响因子：
12.5
通讯作者：
Takahashi JS
中科院分区：
文献类型：
--
作者：
Chen Z;Yoo SH;Takahashi JS
昼夜节律计时系统驱动振荡基因表达来调节基本的细胞和生理过程。当系统受到干扰时，病理后果随之而来，疾病风险上升。据报道，越来越多的小分子调节剂靶向昼夜节律系统。通过高通量筛选鉴定或从已知支架衍生的此类小分子已经显示出作为候选药物改善疾病模型中的生物定时和生理输出的前景。在这篇综述中，我们首先简要介绍了昼夜节律系统，包括核心振荡器和细胞网络。介绍了生物钟调节小分子的研究进展，重点介绍了开发策略和生物功效。我们强调了小分子在生物钟相关疾病中的治疗潜力，包括时差和轮班工作;各种慢性疾病，特别是代谢性疾病;和衰老。新兴的机会，确定和利用时钟调制器作为新的治疗药物进行了讨论。
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.
登录
查看更多内容
影响因子：
8
作者：
Chen, Zheng;Yoo, Seung-Hee;Takahashi, Joseph S.
通讯作者：
Takahashi, Joseph S.
影响因子：
16.6
作者：
Banerjee, Subhashis;Wang, Yongjun;Burris, Thomas P.
通讯作者：
Burris, Thomas P.
影响因子：
64.5
作者：
Balsalobre, A;Damiola, F;Schibler, U
通讯作者：
Schibler, U
影响因子：
9.2
作者：
Balsalobre, A;Marcacci, L;Schibler, U
通讯作者：
Schibler, U
影响因子：
5.3
作者：
Bertolucci, Cristiano;Cavallari, Nicola;Pinotti, Mirko
通讯作者：
Pinotti, Mirko