靶向生物钟进行药物发现的时机已到。
Time to target the circadian clock for drug discovery.
机构信息
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
出版信息
Trends Biochem Sci. 2022 Sep;47(9):745-758. doi: 10.1016/j.tibs.2022.04.009. Epub 2022 May 13.
Abstract
The circadian clock is an intracellular timekeeping device that drives daily rhythms in diverse and extensive processes throughout the body. The clock mechanism comprises a core transcription/translation negative feedback loop that is modulated by a complex set of additional interlocking feedback loops. Pharmacological manipulation of the clock may be valuable for treating many maladies including jet lag, shift work and related sleep disorders, various metabolic diseases, and cancer. We review recent identification of small-molecule clock modulators and discuss the biochemical features of the core clock that may be amenable to future drug discovery.
摘要
生物钟是一种细胞内的计时装置，它驱动着全身各种广泛的过程的日常节律。时钟机制包括一个核心的转录/翻译负反馈回路，该回路受一系列复杂的相互关联的反馈回路的调节。对时钟进行药理学操作可能对治疗许多疾病有价值，包括时差、轮班工作和相关的睡眠障碍、各种代谢疾病和癌症。我们回顾了最近对小分子时钟调节剂的鉴定，并讨论了核心时钟的生化特征，这些特征可能适合未来的药物发现。
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