Small molecule modulators of the circadian molecular clock with implications for neuropsychiatric diseases

Hyo Kyeong Cha, Sooyoung Chung, Hye Young Lim, Jong Wha Jung, Gi Hoon Son

Research output: Contribution to journalReview articlepeer-review

22 Citations (Scopus)


Circadian rhythms regulate many biological processes and play fundamental roles in behavior, physiology, and metabolism. Such periodicity is critical for homeostasis because disruption or misalignment of the intrinsic rhythms is associated with the onset and progression of various human diseases and often directly leads to pathological states. Since the first identification of mammalian circadian clock genes, numerous genetic and biochemical studies have revealed the molecular basis of these cell-autonomous and self-sustainable rhythms. Specifically, these rhythms are generated by two interlocking transcription/translation feedback loops of clock proteins. As our understanding of these underlying mechanisms and their functional outputs has expanded, strategies have emerged to pharmacologically control the circadian molecular clock. Small molecules that target the molecular clock may present novel therapeutic strategies to treat chronic circadian rhythm-related diseases. These pharmaceutical approaches may include the development of new drugs to treat circadian clock-related disorders or combinational use with existing therapeutic strategies to improve efficacy via intrinsic clock-dependent mechanisms. Importantly, circadian rhythm disruptions correlate with, and often precede, many symptoms of various neuropsychiatric disorders such as sleep disorders, affective disorders, addiction-related disorders, and neurodegeneration. In this mini-review, we focus on recent discoveries of small molecules that pharmacologically modulate the core components of the circadian clock and their potential as preventive and/or therapeutic strategies for circadian clock-related neuropsychiatric diseases.

Original languageEnglish
Article number496
JournalFrontiers in Molecular Neuroscience
Publication statusPublished - 2019 Jan 7

Bibliographical note

Funding Information:
This work was supported by the Ministry of Science, the ICT, and the Ministry of Education through the National Research Foundation of Korea (NRF-2015M3A9E7029176 and NRF-2016M3C7A1904340 to GHS, NRF-2014R1A6A3A04054863 to SC). GHS was supported by the Korea University Research Grant.

Publisher Copyright:
© 2019 Cha, Chung, Lim, Jung and Son.


  • Circadian clock
  • Circadian rhythm
  • Circadian rhythm-related disease
  • Cryptochrome
  • ROR
  • Small molecule

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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