A Japanese research team has identified a new compound, Mic-628, that can advance the body's internal clock. The discovery may lead to faster recovery from jet lag and improved adaptation for night-shift workers.
The collaborative group includes Emeritus Professor Tei Hajime from Kanazawa University, Associate Professor Takahata Yoshifumi of The University of Osaka, Professor Numano Rika of Toyohashi University of Technology, and Associate Professor Uriu Koichiro from the Institute of Science Tokyo. They found that Mic-628 selectively induces the mammalian clock gene Per1.
According to the researchers, "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." This mechanism advances both the central clock in the brain's suprachiasmatic nucleus and peripheral clocks in tissues such as the lungs, regardless of when the drug is administered.
In experiments with mice simulating jet lag caused by a six-hour light-dark phase advance, a single oral dose of Mic-628 reduced re-entrainment time from seven days to four. Mathematical modeling indicated that this effect results from negative auto-regulatory feedback involving the PER1 protein.
Adapting to eastward travel or night-shift work requires advancing the internal body clock—a process typically more difficult than delaying it. Current approaches like light therapy or melatonin depend on precise timing and often show inconsistent outcomes. The research team noted that "Mic-628's consistent phase-advance effect, regardless of when it is administered, represents a new pharmacological strategy for resetting the circadian clock."
Future studies will assess Mic-628's safety and efficacy in further animal and human trials. The researchers believe that "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."
The findings were published in 2026 in Proceedings of the National Academy of Sciences of the United States of America (PNAS).
