Scientists discover oral compound that helps “reset” the body clock forward
A potential breakthrough for jet lag and shift work-related sleep disorders
image:
(Upper left) Jet lag from international travel; (Upper right) Mic-628-induced phase advances in behavioral, central, and peripheral circadian clocks; (bottom) Mic-628-CRY recruits CLOCK-BMAL1 dimer to dual E-boxes, inducing Period1.
view moreCredit: Kanazawa University
Key findings
A collaborative team including Emeritus Professor Tei H. (Kanazawa University), Associate Professor Takahata Y. (Osaka University), Professor Numano R. (Toyohashi University of Technology), and Associate Professor Uriu K. (Institute of Science Tokyo) discovered that Mic-628 selectively induces the mammalian clock gene Per1.
Mic-628 works by binding to the repressor protein CRY1, promoting the formation of a CLOCK–BMAL1–CRY1–Mic-628 complex that activates Per1 transcription through a “dual E-box” DNA element. As a result, both the central clock in the brain’s suprachiasmatic nucleus (SCN) and peripheral clocks in tissues such as the lungs were advanced—in tandem and independent of dosing time.
In a simulated jet lag mouse model (6-hour light-dark phase advance), a single oral dose of Mic-628 shortened re-entrainment time from seven days to four. Mathematical modeling revealed that the compound’s stable and unidirectional phase-advancing effect is mediated by a negative auto-regulatory feedback of the PER1 protein itself.
Background and significance
Adapting to eastward travel, such as west-to-east transmeridian flights, or to night-shift work requires advancing the internal clock, a process that normally takes longer and is physiologically harder than delaying it. Existing methods, such as light therapy or melatonin, are heavily constrained by timing and often yield inconsistent results. Mic-628’s consistent phase-advance effect, regardless of when it is administered, represents a new pharmacological strategy for resetting the circadian clock.
What’s next?
The researchers plan to investigate the safety and efficacy of Mic-628 in further animal and human studies. Because it reproducibly advances the body clock through a well-defined molecular mechanism, Mic-628 may serve as a prototype “smart drug” for managing jet lag, shift work-related sleep problems, and other circadian misalignment disorders.
These results will be published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) in 2026.
| About Kanazawa University |
| - Contributing to Society through "Future Oriented Intelligence", Built on an "All Kanazawa University" Approach. Kanazawa University (KU), founded in 1862, is a research university dedicated to education, while opening up its doors to both local and global society. Guided by our vision, "Kokorozashi," we contribute to society through "Future-oriented Intelligence," addressing current challenges and anticipating future ones from both local and global perspectives. KU includes 4 colleges, 20 schools, 7 graduate schools, a hospital, and specialized research centers such as the Cancer Research Institute, a leading hub for research on cancer metastasis and drug development. Over 1,000 researchers drive innovation and international collaboration across diverse fields. KU is advancing research through WPI (World Premier International Research Center Initiative) and J-PEAKS (Program for Forming Japan's Peak Research Universities), accelerating interdisciplinary and international collaborations and innovations. Learn more here: https://www.kanazawa-u.ac.jp/en/ |
About The University of Osaka
The University of Osaka was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world. Now, The University of Osaka is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.
Learn more here:
https://resou.osaka-u.ac.jp/en
Journal
Proceedings of the National Academy of Sciences
Article Title
A Period1 inducer specifically advances circadian clock in mice
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