Chrono-Drug Discovery and Development Based on Circadian Rhythm of Molecular, Cellular and Organ Level

Jun 3, 2021Biological & pharmaceutical bulletin

Drug Discovery and Development Based on Daily Biological Rhythms from Molecules to Organs

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Clock genes are associated with sleep disorders, metabolic syndromes, and cancer diseases.

The circadian pacemaker in mammals is the paired suprachiasmatic nuclei (SCN).
Monitoring and manipulating circadian rhythms may enhance chronopharmacotherapy.
Drug delivery systems designed to align with circadian rhythms are referred to as Chrono-DDS.
New drugs targeting clock genes are being developed for disease management in humans.
Circadian dynamics of cancer stem cells are influenced by the tumor microenvironment, which may aid in chronotherapy for triple-negative breast cancer.
A novel inhibitor of cell cycle regulatory factors has been identified that reduces renal inflammation in a mouse model of chronic kidney disease (CKD).

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The paired suprachiasmatic nuclei (SCN) is the circadian pacemaker in mammals. Clock genes ultimately regulates a vast array of circadian rhythms involved in biological, physiological and behavioral process. The clock genes are closely related to sleep disorders, metabolic syndromes, and cancer diseases. Monitoring rhythm, overcoming rhythm disruption, and manipulating rhythm from the perspective of the clock genes play an important role to improve chronopharmacotherapy. Such an approach should be achieved by overcoming the new challenges in drug delivery systems that match the circadian rhythm (Chrono-DDS). Gene and antibody delivery, targeting specific molecules for certain diseases have been focused in recent studies on pharmacotherapy. One of important candidates should also be clock genes. New drugs targeting the molecular clock are being developed to manage diseases in humans. The circadian dynamics of cancer stem cells are controlled by the tumor microenvironment and provide proof for its implication in chronotherapy against triple-negative breast cancer. To examine the relationship between the circadian clock and chronic kidney disease (CKD) exacervation leads to clarify the novel molecular mechanisms causing renal malfunction in mice with CKD. A novel inhibitor of cell cycle regulatory factors has been identified and the inhibitor repressed renal inflammation in a CKD mouse model. Therefore, this review aims to introduce the role of the molecular clock in the time-dependent dosing changes in the therapeutic effect and safety of a drug and the possibility of drug discovery and development based on the molecular clock.

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Chrono-Drug Discovery and Development Based on Circadian Rhythm of Molecular, Cellular and Organ Level

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