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Pharmacological Interventions to Circadian Clocks and Their Molecular Bases.
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.jmb.2020.01.003 Simon Miller 1 , Tsuyoshi Hirota 1
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2020-01-10 , DOI: 10.1016/j.jmb.2020.01.003 Simon Miller 1 , Tsuyoshi Hirota 1
Affiliation
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Daily physiological rhythms are regulated by the body's internal timekeeper known as the circadian clock. Expression, post-translational modification, and degradation of clock proteins constituting the circadian clock are precisely controlled in a rhythmic manner. Perturbation of these processes by nature and nurture results in physiological dysfunction and diseases. Small-molecule modulators of clock or clock-related proteins can adjust clock functions, and thus represent a promising method of therapeutic treatment for a range of clock-related diseases. In this review, we will introduce the identification and development of small-molecule compounds that target clock proteins, as well as X-ray crystal structures of protein-compound complexes that facilitate the understanding of clock protein regulation and drug derivatization. Furthermore, we describe the effects of these compounds in a diseased setting and discuss the therapeutic potential of clock modulators.
中文翻译：
昼夜节律及其分子基础的药理干预。
日常生理节律由人体内部的钟表（昼夜节律时钟）调节。以节律的方式精确控制构成昼夜节律时钟的时钟蛋白的表达，翻译后修饰和降解。这些过程的天性和养分扰动会导致生理功能障碍和疾病。时钟或与时钟相关的蛋白质的小分子调节剂可以调节时钟功能，因此代表了一系列与时钟相关的疾病的有前途的治疗方法。在这篇综述中，我们将介绍靶向时钟蛋白的小分子化合物的鉴定和开发，以及有助于理解时钟蛋白调节和药物衍生作用的蛋白化合物复合物的X射线晶体结构。此外，
更新日期：2020-01-11
中文翻译：
昼夜节律及其分子基础的药理干预。
日常生理节律由人体内部的钟表（昼夜节律时钟）调节。以节律的方式精确控制构成昼夜节律时钟的时钟蛋白的表达，翻译后修饰和降解。这些过程的天性和养分扰动会导致生理功能障碍和疾病。时钟或与时钟相关的蛋白质的小分子调节剂可以调节时钟功能，因此代表了一系列与时钟相关的疾病的有前途的治疗方法。在这篇综述中，我们将介绍靶向时钟蛋白的小分子化合物的鉴定和开发，以及有助于理解时钟蛋白调节和药物衍生作用的蛋白化合物复合物的X射线晶体结构。此外，
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