Discovery: Novel Compound Mic-628 Selectively Induces Clock Gene Per1

A collaborative research team, including Emeritus Professor Tei Hajime (Kanazawa University), Associate Professor Takahata Yoshifumi (The University of Osaka), Professor Numano Rika (Toyohashi University of Technology), and Associate Professor Uriu Koichiro (Institute of Science Tokyo), has discovered that the compound Mic-628 selectively induces the mammalian clock gene Per1.

The compound Mic-628 selectively induces the mammalian clock gene Per1.

Mic-628 functions by binding to the repressor protein CRY1. This binding promotes the formation of a CLOCK-BMAL1-CRY1-Mic-628 complex, which subsequently activates Per1 transcription through a "dual E-box" DNA element. This process led to the advancement of both the central clock in the brain's suprachiasmatic nucleus (SCN) and peripheral clocks in tissues like the lungs, independently of the dosing time.

In a simulated jet lag mouse model, where a six-hour light-dark phase advance was applied, a single oral dose of Mic-628 reduced the re-entrainment time from seven days to four. Mathematical modeling suggests that the compound's stable and unidirectional phase-advancing effect is mediated by a negative auto-regulatory feedback loop involving the PER1 protein itself.

In a simulated jet lag mouse model, a single oral dose of Mic-628 reduced the re-entrainment time from seven days to four.