Expert Opin Drug Discov. 2012 Jul;7(7):535-41. doi: 10.1517/17460441.2012.689283. Epub 2012 Jun 2.
Drug discovery scientists, faced with the myriad challenges involved in developing novel therapeutics as medicines, have tended to overlook the question of the most beneficial time to administer the drug. Recent developments in our understanding of circadian biology and the availability of tools to characterise the molecular clock indicate that time and duration of dosing may have profound consequences for the efficacy and safety of new and existing therapeutic agents. Progress in the field also suggests that many key physiological mechanisms are remarkably dependent on the circadian clock. It has also become clear that a number of diseases with important unmet medical need display marked circadian variation in their symptoms and severity. These discoveries now reveal opportunities for new therapeutic strategies to be developed that act by modulation of biological rhythms. These novel therapeutic approaches are likely to be facilitated by the continuing development of chemical probes and synthetic ligands targeted to an increasing number of the key proteins that regulate the molecular clock.
药物研发科学家在开发新型治疗药物时面临着无数的挑战,往往忽略了给药的最佳时间问题。我们对生物钟的理解的最新进展以及表征分子钟的工具的可用性表明,给药的时间和持续时间可能对新的和现有的治疗药物的疗效和安全性产生深远的影响。该领域的进展还表明,许多关键的生理机制非常依赖于生物钟。此外,许多具有重要未满足医疗需求的疾病在其症状和严重程度方面表现出明显的昼夜节律变化。这些发现现在为开发新的治疗策略提供了机会,这些策略通过调节生物节律来发挥作用。随着针对调节分子钟的关键蛋白数量不断增加的化学探针和合成配体的不断开发,这些新型治疗方法可能会得到促进。