KL001

• CAS: 309928-48-1
• Catalog Number: ACM309928481
• Category: Others
• Molecular Weight: 398.48
• Molecular Formula: C21H22N2O4S
• Description: KL001 is a Cryptochrome protein (CRY) stabilizer. KL001 prevented ubiquitin-dependent degradation of CRY, resulting in lengthening of the circadian period. In combination with mathematical modeling, our studies using KL001 revealed that CRY1 and CRY2 share a similar functional role in the period regulation. Furthermore, KL001-mediated CRY stabilization inhibited glucagon-induced gluconeogenesis in primary hepatocytes. KL001 thus provides a tool to study the regulation of CRY-dependent physiology and aid development of clock-based therapeutics of diabetes.
• Synonyms: KL001; KL-001; KL 001
• IUPAC Name: N-[3-(9H-Carbazol-9-yl)-2-hydroxypropyl]-N-(2-furanylmethyl)methanesulfonamide
• Canonical SMILES: CS(=O)(N(CC(O)CN1C2=C(C3=C1C=CC=C3)C=CC=C2)CC4=CC=CO4)=O
• InChI: InChI=1S/C21H22N2O4S/c1-28(25,26)22(15-17-7-6-12-27-17)13-16(24)14-23-20-10-4-2-8-18(20)19-9-3-5-11-21(19)23/h2-12,16,24H,13-15H2,1H3
• InChI Key: OQAFDLPAPSSOHY-UHFFFAOYSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: KL001 is a first-in-class cryptochrome stabilizer which specifically interacts with CRY1 and CRY2 and prevents ubiquitin-dependent degradation of CRY, resulting in lengthening of the circadian period.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 63.30; H, 5.57; N, 7.03; O, 16.06; S, 8.05
• Exact Mass: 398.13
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: KL001 at 2.5 µM and 10 µM was well tolerated by tendon fibroblasts but led to arrhythmic bioluminescence in PER2::LUC tendon fibroblasts. The addition of KL001 to control tendon fibroblasts led to increased steady-state levels of Sec61a2, Mia3, Pde4d and Vps33b transcripts as well as increased numbers of collagen fibres per cell. Conversely, KL001 did not restore rhythmic bioluminescence to PER2::LUC::ClockΔ19 fibroblasts, and the addition of KL001 to ClockΔ19 fibroblasts resulted in decreased levels of Mia3, Serpinh1, Pde4d and Vps33b as well as a decrease in the number of collagen fibres per cell in these cells. The increase in collagen fibre numbers in wild-type cells treated with KL001 (which became arrhythmic) and the decrease in collagen fibre numbers in ClockΔ19 cells treated with KL001 indicates that rhythmicity in the secretory pathway is required for collagen fibre homeostasis.; Reference: Nat Cell Biol. 2020 Jan;22(1):74-86. https://pubmed.ncbi.nlm.nih.gov/31907414/
• In Vivo Activity: Statistically significant results of the assessment of differences in indicators in groups receiving activator KL001 at different concentrations indicate the ability of KL001 to prolong the lifespan of Drosophila. Therefore, for a concentration of 5 μM, an increase of 3.5% is shown for the average lifespan, p < 0.00001, according to the χ2-test), 2% for median lifespan (50% of population mortality), p < 0.001, in accordance to the Gehan-Breslow-Wilcoxon test. The age of 90% mortality of the population that received 5μM KL001 with food increased by 14%, p < 0.05, is in accordance to the Wang-Allison test. The time of 90% mortality of the population was subjected to a statistically significant effect of KL001 in all variants of the experiment; there was an increase in the indicator by 9-14%, p < 0.05, according to the Wang-Allison test. This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos' utilization in starvation conditions which is activated by dCRY binding KL001.; Reference: Clocks Sleep. 2021 Aug 20;3(3):429-441. https://pubmed.ncbi.nlm.nih.gov/34449576/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).