KL001
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MedKoo CAT#: 522570

CAS#: 309928-48-1

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.


Chemical Structure

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KL001
CAS# 309928-48-1

Theoretical Analysis

MedKoo Cat#: 522570
Name: KL001
CAS#: 309928-48-1
Chemical Formula: C21H22N2O4S
Exact Mass: 398.13
Molecular Weight: 398.477
Elemental Analysis: C, 63.30; H, 5.57; N, 7.03; O, 16.06; S, 8.05

Price and Availability

Size Price Availability Quantity
50.0mg USD 450.0 2 Weeks
100.0mg USD 750.0 2 Weeks
200.0mg USD 1250.0 2 Weeks
500.0mg USD 2850.0 2 Weeks
1.0g USD 3850.0 2 Weeks
2.0g USD 6250.0 2 Weeks
Bulk inquiry

Synonym: KL001; KL-001; KL 001.

IUPAC/Chemical Name: N-[3-(9H-Carbazol-9-yl)-2-hydroxypropyl]-N-(2-furanylmethyl)methanesulfonamide

InChi Key: OQAFDLPAPSSOHY-UHFFFAOYSA-N

InChi Code: 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

SMILES Code: CS(=O)(N(CC(O)CN1C2=C(C3=C1C=CC=C3)C=CC=C2)CC4=CC=CO4)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: 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.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

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.
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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 32.46 81.47

Preparing Stock Solutions

The following data is based on the product molecular weight 398.477 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Chang J, Garva R, Pickard A, Yeung CC, Mallikarjun V, Swift J, Holmes DF, Calverley B, Lu Y, Adamson A, Raymond-Hayling H, Jensen O, Shearer T, Meng QJ, Kadler KE. Circadian control of the secretory pathway maintains collagen homeostasis. Nat Cell Biol. 2020 Jan;22(1):74-86. doi: 10.1038/s41556-019-0441-z. Epub 2020 Jan 6. PMID: 31907414. 2. Hirota T, Lee JW, St John PC, Sawa M, Iwaisako K, Noguchi T, Pongsawakul PY, Sonntag T, Welsh DK, Brenner DA, Doyle FJ 3rd, Schultz PG, Kay SA. Identification of small molecule activators of cryptochrome. Science. 2012 Aug 31;337(6098):1094-7. doi: 10.1126/science.1223710. Epub 2012 Jul 12. PMID: 22798407; PMCID: PMC3589997. 3.Solovev IA, Shaposhnikov MV, Moskalev AA. Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster. Clocks Sleep. 2021 Aug 20;3(3):429-441. doi: 10.3390/clockssleep3030030. PMID: 34449576; PMCID: PMC8395451. 4. Iida M, Nakane Y, Yoshimura T, Hirota T. Effects of Cryptochrome-modulating compounds on circadian behavioral rhythms in zebrafish. J Biochem. 2021 Sep 16:mvab096. doi: 10.1093/jb/mvab096. Epub ahead of print. Erratum in: J Biochem. 2022 Feb 18;: PMID: 34528676.
In vitro protocol: 1. Chang J, Garva R, Pickard A, Yeung CC, Mallikarjun V, Swift J, Holmes DF, Calverley B, Lu Y, Adamson A, Raymond-Hayling H, Jensen O, Shearer T, Meng QJ, Kadler KE. Circadian control of the secretory pathway maintains collagen homeostasis. Nat Cell Biol. 2020 Jan;22(1):74-86. doi: 10.1038/s41556-019-0441-z. Epub 2020 Jan 6. PMID: 31907414. 2. Hirota T, Lee JW, St John PC, Sawa M, Iwaisako K, Noguchi T, Pongsawakul PY, Sonntag T, Welsh DK, Brenner DA, Doyle FJ 3rd, Schultz PG, Kay SA. Identification of small molecule activators of cryptochrome. Science. 2012 Aug 31;337(6098):1094-7. doi: 10.1126/science.1223710. Epub 2012 Jul 12. PMID: 22798407; PMCID: PMC3589997.
In vivo protocol: 1.Solovev IA, Shaposhnikov MV, Moskalev AA. Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster. Clocks Sleep. 2021 Aug 20;3(3):429-441. doi: 10.3390/clockssleep3030030. PMID: 34449576; PMCID: PMC8395451. 2.Iida M, Nakane Y, Yoshimura T, Hirota T. Effects of Cryptochrome-modulating compounds on circadian behavioral rhythms in zebrafish. J Biochem. 2021 Sep 16:mvab096. doi: 10.1093/jb/mvab096. Epub ahead of print. Erratum in: J Biochem. 2022 Feb 18;: PMID: 34528676.

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1: Lee JW, Hirota T, Kumar A, Kim NJ, Irle S, Kay SA. Development of
Small-Molecule Cryptochrome Stabilizer Derivatives as Modulators of the Circadian
Clock. ChemMedChem. 2015 Sep;10(9):1489-97. doi: 10.1002/cmdc.201500260. Epub
2015 Jul 14. PubMed PMID: 26174033; PubMed Central PMCID: PMC4576822.

2: Oshima T, Yamanaka I, Kumar A, Yamaguchi J, Nishiwaki-Ohkawa T, Muto K,
Kawamura R, Hirota T, Yagita K, Irle S, Kay SA, Yoshimura T, Itami K. C-H
activation generates period-shortening molecules that target cryptochrome in the
mammalian circadian clock. Angew Chem Int Ed Engl. 2015 Jun 8;54(24):7193-7. doi:
10.1002/anie.201502942. Epub 2015 May 8. PubMed PMID: 25960183.

3: St John PC, Hirota T, Kay SA, Doyle FJ 3rd. Spatiotemporal separation of PER
and CRY posttranslational regulation in the mammalian circadian clock. Proc Natl
Acad Sci U S A. 2014 Feb 4;111(5):2040-5. doi: 10.1073/pnas.1323618111. Epub 2014
Jan 21. PubMed PMID: 24449901; PubMed Central PMCID: PMC3918757.

4: Kelleher FC, Rao A, Maguire A. Circadian molecular clocks and cancer. Cancer
Lett. 2014 Jan 1;342(1):9-18. doi: 10.1016/j.canlet.2013.09.040. Epub 2013 Oct 4.
Review. PubMed PMID: 24099911.

5: Nangle S, Xing W, Zheng N. Crystal structure of mammalian cryptochrome in
complex with a small molecule competitor of its ubiquitin ligase. Cell Res. 2013
Dec;23(12):1417-9. doi: 10.1038/cr.2013.136. Epub 2013 Oct 1. PubMed PMID:
24080726; PubMed Central PMCID: PMC3847572.

6: Sklan A. Discovery of activator for cryptochrome may shape development of
metabolic drugs. Future Med Chem. 2012 Sep;4(13):1660. PubMed PMID: 23087927.

7: Hirota T, Lee JW, St John PC, Sawa M, Iwaisako K, Noguchi T, Pongsawakul PY,
Sonntag T, Welsh DK, Brenner DA, Doyle FJ 3rd, Schultz PG, Kay SA. Identification
of small molecule activators of cryptochrome. Science. 2012 Aug
31;337(6098):1094-7. doi: 10.1126/science.1223710. Epub 2012 Jul 12. PubMed PMID:
22798407; PubMed Central PMCID: PMC3589997.

KL001

50.0mg / USD 450.0