KL001 is a small molecule that specifically interacts with cryptochrome (CRY). KL001 prevented ubiquitin-dependent degrdation of CRY, resulting in lengthening of the circadian period. KL001-mediated CRY stabilization inhibited glucagon-induced gluconeogenesis in primary hepatocytes making it a tool to study the regulation of CRY-dependent physiology and aid development of clock-based therapeutics of diabetes.
Biochem/physiol Actions
KL001 stabilizes cryptochrome (CRY), preventing ubiquitin-dependent degradation. CRY proteins are part of a feedback loop, acting as transcription repressors to inhibit CLOCK-BMAL1 components of the circadian clock. KL001 stabilization of CRY proteins results in lengthening of the circadian period, and also inhibited glucagon-induced gluconeogenesis in primary hepatocytes. Other compounds affecting circadian rhythms include Casein kinase I (CKI) inhibitors such as longdaysin (Sigma Prod. No. SML0127) and synthetic ligands for the nuclear receptors REV-ERB such as SR8278 (Sigma Prod. No. S9576), but KL001 appears to be the first small molecule that specifically acts on CRY proteins.
