KL001 Chemical Properties

storage temp. 

2-8°C

solubility 

DMSO: soluble20mg/mL, clear

form 

powder

color 

white to beige

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.

Safety Information

Hazard Codes 

Xn

Risk Statements 

22

WGK Germany 

3

KL001 Usage And Synthesis

Description

KL-001 (309928-48-1) is a novel tool that specifically interacts with cryptochrome (CRY) preventing its ubiquitin-dependent degradation resulting in lengthening of the circadian period. KL-001-mediated CRY stabilization inhibits glucagon-induced gluconeogenesis in primary hepatocytes.1?Binds to the FAD-binding pocket of CRY2 as determined by co-crystal structure.2?KL-001 induces an increase in period along with simultaneous reduction in amplitude of circadian reporter expression3 in mammalian cells.

Uses

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.

storage

Store at +4°C

References

1) Hirota et al. (2012), Identification of small molecule activators of cryptochrome; Science, 337 1094 2) Nangle et al. (2013), Crystal structure of mammalian cryptochrome in complex with a small molecule competitor of its ubiquitin ligase; Cell Res., 23 1417 3) St. John et al. (2014), Spatiotemporal separation of PER and CRY posttranslational regulation in the mammalian circadian clock; Proc. Natl. Acad. Sci. USA, 11 2040

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