A Japanese research team has discovered a new agent that can shift the body’s internal clock forward. This offers hope for faster recovery from jet lag and better adaptation to night shift work. The agent Mic-628 specifically activates the transcription of the “clock gene” Period1 (Per1). When administered orally to mice, it shifted their internal clocks and activity rhythms regardless of the time of administration. The findings suggest a new approach to controlling circadian rhythms through medication rather than light exposure.

The team led by Emeritus Professor Tei Hajime from Kanazawa University, Associate Professor Takahata Yoshifumi from the University of Osaka, Professor Numano Rika from Toyohashi University of Technology and Associate Professor Uriu Koichiro from the Institute of Science Tokyo discovered that Mic-628 selectively induces the mammalian clock gene Per1. Mic-628 binds to the repressor protein CRY1 and promotes the formation of a CLOCK-BMAL1-CRY1-Mic-628 complex that activates Per1 transcription via a dual E-Box DNA element. As a result, both the central clock in the suprachiasmatic nucleus of the brain and peripheral clocks in tissues such as the lungs were shifted forward, synchronously and independently of the time of administration.

In a simulated jet lag model in mice with a six-hour advance of the light-dark phase, a single oral dose of Mic-628 reduced the re-entrainment time from seven to four days. Mathematical models showed that the stable and unidirectional phase-shift effect is mediated by a negative autoregulatory feedback of the PER1 protein.

Adapting to eastward travel or night shift work requires a forward shift in the internal clock, which is physiologically more difficult and time-consuming than a delay. Existing methods such as light therapy or melatonin are limited in time and often produce inconsistent results. The consistent phase-shift effect of Mic-628 regardless of the time of administration represents a new pharmacological strategy for resetting the circadian clock.

The researchers plan to investigate the safety and efficacy of Mic-628 in further animal and human studies. Due to the reproducible forward shift of the circadian clock by a defined molecular mechanism, Mic-628 could serve as a prototype for a smart drug to treat jet lag, shiftwork-related sleep disorders, and other circadian maladaptations.

The results were published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) in 2026.

Founded in 1931 as one of Japan’s seven imperial universities, the University of Osaka is now a leading comprehensive university with a wide range of subjects. It combines strength in basic research with applied technology for positive economic impact. The university uses its role as the designated national university corporation of the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human well-being, sustainable social development and social transformation.

Original paper:

Title: A Period1 inducer specifically advances circadian clock in mice
Journal: Proceedings of the National Academy of Sciences
Authors: Yoshifumi Takahata, Yuki Kasashima, Takuya Yoshioka, Shusei Yashiki, Justina Kulikauskaite, Tomoaki Matsuura, Yuki Ohba, Hideaki Hasegawa, Naoki Yuri, Nagisa Iwai, Nanako Otsu, Mikiya Kitakata, Yuta Kitaguchi, Haruki Furune, Chihiro Omori, Mutsumi Mukai, Yuki Komamura-Kohno, Yi-Ying Huang, Matsumi Hirose, Nobuya Koike, Yoichi Yamada, Kazuo Nakazawa, Kumiko Ui- Tei, Yoshiyuki Sakaki, Rika Numano, Koichiro Uriu & Hajime Tei
DOI: 10.1073/pnas.2509943123

Editor: X-Press Journalistenbüro GbR

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