The cryptochrome proteins CRY1 and CRY2, which play central roles in maintaining the circadian clock, are expressed and then degraded in a rhythmic pattern. KL001 is a cell-permeable carbazolic compound which directly interacts with and stabilizes CRY1 and CRY2, preventing ubiquitin-dependent degradation while lengthening the circadian period (IC50 = 0.82-14 μM). As the expression of some gluconeogenic genes is both circadian and cryptochrome-dependent, KL001 effectively inhibits glucagon-induced gluconeogenesis in primary hepatocytes. This product can be used to study the regulation of cryptochrome-dependent physiology and aid in the development of clock-based therapeutics of diabetes.
