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Editorial
. 2017 Dec;12(12):1181-1185.
doi: 10.1080/17460441.2017.1378179. Epub 2017 Sep 11.

What's next for chronobiology and drug discovery

Zheng Chen  1
Affiliations
Editorial

What's next for chronobiology and drug discovery

Zheng Chen. Expert Opin Drug Discov. 2017 Dec.
No abstract available

Keywords: Circadian clock; chronotherapy and chronomedicine; clock-modulating molecules; clock-related diseases and aging; human trials.

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Conflict of interest statement

Declaration of Interest:

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
The circadian oscillator and representative drug candidates. The cell-autonomous core oscillator consists of interlocked feedback loops. In core and secondary loops, positive and negative factors form transcription-translation negative feedback. Several other feedback loops (e.g., DBP loop) have been shown to superimpose on this basic framework to fine-tune circadian oscillation. The circadian clock, including both systemic control originated from the SCN and local oscillators, drives downstream gene expression, either directly via circadian response elements including E-box, RORE, and D-box, recognized by CLOCK/BMAL1, REV-ERBs and RORs, and DBP respectively, or indirectly by clock-controlled transcription factors, epigenetic regulators and post-transcriptional and post-translational machineries. A number of small molecules have been identified or developed to target core clock components or proximal regulatory factors (highlighted in red with arrows). Adapted from [5] permission of Frontiers in Neurology via the Creative Commons CC-BY license.
Figure 2.
Figure 2.
Four key areas of interests in drug discovery for chronomedicine. Please see text for details. PPI: protein-protein interaction. PK: pharmacokinetics. Human trials are of critical urgency and importance to validate clock-targeting therapeutics. Established drugs or natural products with known PK and safety profiles are ideally positioned to advance to trials.
See this image and copyright information in PMC

References

    1. Takahashi JS. Transcriptional architecture of the mammalian circadian clock. Nat Rev Genet 2017. March;18(3):164–79. - PMC - PubMed
    1. Zhang R, Lahens NF, Ballance HI, Hughes ME, Hogenesch JB. A circadian gene expression atlas in mammals: implications for biology and medicine. Proceedings of the National Academy of Sciences of the United States of America 2014. November 11;111(45):16219–24. A comprehensive characterization of circadian gene expression throughout the body and important insights on circadian expression of drug targets. - PMC - PubMed
    1. Bass J, Lazar MA. Circadian time signatures of fitness and disease. Science 2016. November 25;354(6315):994–99. - PubMed
    1. Schroeder AM, Colwell CS. How to fix a broken clock. Trends Pharmacol Sci 2013. November;34(11):605–19. - PMC - PubMed
    1. Gloston GF, Yoo SH, Chen ZJ. Clock-Enhancing Small Molecules and Potential Applications in Chronic Diseases and Aging. Front Neurol 2017;8:100. - PMC - PubMed

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