Scientists have identified a promising new compound, Mic-628, that can reliably shift the body’s internal clock forward—something that’s notoriously hard to do. By targeting a key clock-control protein, Mic-628 jump-starts the gene that sets daily rhythms, synchronizing both the brain’s master clock and clocks throughout the body. In mice experiencing simulated jet lag, a single dose cut recovery time nearly in half.
The researchers found that Mic-628 works by attaching to CRY1, a protein that normally suppresses clock gene activity. This interaction encourages the formation of a larger molecular complex known as CLOCK-BMAL1-CRY1-Mic-628. Once formed, this complex switches on Per1 by acting at a specific DNA site called a "dual E-box." Through this mechanism, Mic-628 shifts the timing of both the brain's master clock located in the suprachiasmatic nucleus (SCN) and clocks in other organs, including the lungs. Notably, these clock shifts occurred together and did not depend on when the compound was given.
Adjusting to earlier schedules, such as traveling east across time zones or working night shifts, requires the body clock to move forward. This type of adjustment is typically slower and more stressful for the body than delaying the clock. Common approaches like light exposure or melatonin depend heavily on precise timing and often produce uneven results. Because Mic-628 consistently advances the clock regardless of dosing time, it offers a fundamentally different drug-based approach to circadian reset.
The researchers plan to continue studying Mic-628 to better understand its safety and effectiveness in additional animal studies and in humans. Since the compound reliably moves the body clock forward through a clearly defined biological pathway, it could become a model "smart drug" for addressing jet lag, sleep problems linked to shift work, and other disorders caused by circadian misalignment.
