Cryptochrome dyes are a kind of flavin sensitive to blue light and exist in plants and animals. Specifically, cryptochroma involves the circadian rhythms of plants and animals, and may also involve magnetic field sensing in many species. In insects and plants, CRY1 regulates the biological clock in a light-dependent manner. While in mammals, CRY1 and CRY2 are photo independent inhibitors of the clock-bmal1 component. In addition to chlorophyll, cryptochrome is the only protein known to form photoinduced free radical pairs in vivo. Besides, circadian rhythms are produced autonomously through the transcriptional regulatory network of clock genes. In the core feedback loop, transcription factors clock and BMAL1 activate the expression of period and cryptochrome genes. After translation and nuclear localization, per and Cry proteins inhibited the function of clock-bmal1, resulting in the expression of rhythmic genes. KL001 is a cryptochrome protein (CRY) stabilizer which specifically interacts with CRY1 and CRY2.
KL001, a cryptochrome protein (CRY) stabilizer, specifically interacts with CRY1 and CRY2.
How does KL001 work on the CRY? Let’s study it together. In the beginning, KL001 is a cryptochrome protein (CRY) stabilizer which specifically interacts with CRY1 and CRY2. Moreover, KL001 prevents ubiquitin-dependent degradation of CRY, resulting in lengthening of the circadian period. Furthermore, KL001 has the potential to control fasting hormone-induced gluconeogenesis.
Secondly, KL001 (0.03-71 μM) causes circadian period lengthening and amplitude reduction in a dose-dependent manner in stable U2OS reporter cell lines harboring Bmal1-dLuc or Per2-dLuc. Meanwhile, KL001 (2-8 μM; 18 h) represses glucagon-dependent induction of Pck1 and G6pc genes in a dose-dependent manner. Nonetheless, KL001 has no effect on their basal expression in mouse primary hepatocyte.
All in all, KL001 is a cryptochrome protein (CRY) stabilizer which specifically interacts with CRY1 and CRY2.