No More Jet Lag: New Oral Compound Helps “Reset” the Body’s Internal Clock

A new oral compound can reset the circadian clock independent of timing, dramatically speeding recovery from jet lag in animal models.

Most people have felt it: that foggy, out-of-sync sensation after a late-night flight, an all-nighter, or a sudden switch to overnight work. It happens because the body runs on a built-in 24-hour timekeeper, the circadian rhythm, that helps coordinate sleep, alertness, hormone release, metabolism, and even body temperature. When your schedule changes faster than your internal clock can adapt, the result is jet lag or shift-work misalignment: insomnia at bedtime, exhaustion during the day, and sluggish performance that can linger for days.

Light is the main cue that resets this clock, which is why bright-light therapy and carefully timed melatonin are often recommended. But those approaches can be fussy. Timing matters a lot, individual responses vary, and real life doesn’t always cooperate with a strict light schedule.

Now, researchers from the University of Osaka, Kanazawa University, Toyohashi University of Technology, and the Institute of Science Tokyo report a potential chemical alternative: a new oral compound called Mic-628 that can reliably shift the body’s internal clock forward. The discovery points to a possible new way to help people recover faster from jet lag and adapt to night-shift schedules.

A chemical shortcut to resetting the body clock

Mic-628 acts by turning on the activity of a key clock gene known as Period1 (Per1). It does this by binding to CRY1, a protein that normally suppresses Per1, allowing the gene to become active in both the brain’s master clock and in clocks found throughout the body.

In experiments with mice, the compound advanced circadian timing no matter when it was given. This sets it apart from approaches such as light exposure or melatonin, which must be carefully timed and often produce uneven results.

In a simulated jet lag mouse model, a single dose of Mic-628 reduced the re-entrainment time from seven days to just four. This stable and unidirectional advancement capability represents a groundbreaking strategy for resetting the circadian clock, especially for challenging adjustments like eastward travel or graveyard shifts.

Toward a new class of circadian medicine

Researchers envision Mic-628 as a prototype “smart drug” for managing various circadian misalignment disorders. Further animal and human studies are planned to assess its safety and efficacy.

Reference: “A Period1 inducer specifically advances circadian clock in mice” by 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 and Hajime Tei, 23 January 2026, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2509943123

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