KL201 a circadian clock modulator, is a isoform-selective cryptochrome 1 (CRY1) stabilizer. KL201 has no stabilizing effect on CRY2. KL201 lengthens the period of circadian rhythms in cells and tissues[1].
KL201 causes dose-dependent lengthening of circadian period in Bmal1-dLuc reporter cells, and in cells with another circadian reporter Per2-dLuc. KL201 suppresses the intensity of Per2-dLuc reporter much more than that of Bmal1-dLuc, without affecting cellular viability[1].KL201 binds to CRY1 in overlap with FBXL3, a subunit of ubiquitin ligase complex, and the effect of KL201 is blunted by knockdown of FBXL3[1].KL201 lengthened circadian period and suppressed the intensity of Per2::Luc knockin reporter in mouse lung primary explants[1].
[1]. Simon Miller, et al. An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals. Cell Chem Biol. 2020 Sep 17;27(9):1192-1198.e5.