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.
The researchers 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.
