KL001 | CAS#309928-48-1 | Cryptochrome protein (CRY) stabilizer

KL001
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WARNING: This product is for research use only, not for human or veterinary use.

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

KL001

CAS# 309928-48-1

Product data Instruction

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
50mg	USD 450	2 Weeks
100mg	USD 750	2 Weeks
200mg	USD 1250	2 Weeks
500mg	USD 2850	2 Weeks
1g	USD 3850	2 Weeks
2g	USD 6250	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

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

More Info:

Product Data:

Product Data

Instruction:

View handling instruction

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	32.5	81.47

Preparing Stock Solutions

The following data is based on the product molecular weight 398.48 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.

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.

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