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

MedKoo Cat#: 522570 | Name: KL001

Description:

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

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

Theoretical Analysis

MedKoo Cat#: 522570

Name: KL001

CAS#: 309928-48-1

Chemical Formula: C21H22N2O4S

Exact Mass: 398.1300

Molecular Weight: 398.48

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 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,850.00	2 Weeks
1g	USD 3,850.00	2 Weeks
2g	USD 6,250.00	2 Weeks

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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/

	Solvent	mg/mL	mM
Solubility
	DMSO	32.5	81.47

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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:

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.

1: Murdoch SÓ, Aiello EM, Doyle FJ 3rd. Pharmacokinetic Model-Based Control across the Blood-Brain Barrier for Circadian Entrainment. Int J Mol Sci. 2023 Oct 2;24(19):14830. doi: 10.3390/ijms241914830. PMID: 37834278; PMCID: PMC10573769. 2: Li W, Xiong X, Kiperman T, Ma K. Transcription Repression of CRY2 via PER2 Interaction Promotes Adipogenesis. Mol Cell Biol. 2023;43(10):500-514. doi: 10.1080/10985549.2023.2253710. Epub 2023 Oct 11. PMID: 37724597; PMCID: PMC10569361. 3: Duraisamy SK, Srinivasan A, Sundar IK. House dust mite and Th2 cytokine- mediated epithelial barrier dysfunction attenuation by KL001 in 16-HBE cells. Tissue Barriers. 2024 Jan 2;12(1):2203841. doi: 10.1080/21688370.2023.2203841. Epub 2023 Apr 20. PMID: 37079442; PMCID: PMC10832928. 4: Li W, Xiong X, Kiperman T, Ma K. Transcription repression of Cry2 via Per2 interaction promotes adipogenesis. bioRxiv [Preprint]. 2023 Mar 13:2023.03.12.532323. doi: 10.1101/2023.03.12.532323. Update in: Mol Cell Biol. 2023 Sep 19;:1-15. PMID: 36993226; PMCID: PMC10054956. 5: Ge YX, Zhuang HJ, Zhang TW, Liang HF, Ding W, Zhou L, Dong ZR, Hu ZC, Chen Q, Dong J, Jiang LB, Yin XF. Precise manipulation of circadian clock using MnO2 nanocapsules to amplify photodynamic therapy for osteosarcoma. Mater Today Bio. 2023 Jan 26;19:100547. doi: 10.1016/j.mtbio.2023.100547. PMID: 36896415; PMCID: PMC9988696. 6: Gao R, Zhang X, Zou K, Meng D, Lv J. Cryptochrome 1 activation inhibits melanogenesis and melanosome transport through negative regulation of cAMP/PKA/CREB signaling pathway. Front Pharmacol. 2023 Feb 6;14:1081030. doi: 10.3389/fphar.2023.1081030. PMID: 36814484; PMCID: PMC9939694. 7: Miller S, Kesherwani M, Chan P, Nagai Y, Yagi M, Cope J, Tama F, Kay SA, Hirota T. CRY2 isoform selectivity of a circadian clock modulator with antiglioblastoma efficacy. Proc Natl Acad Sci U S A. 2022 Oct 4;119(40):e2203936119. doi: 10.1073/pnas.2203936119. Epub 2022 Sep 26. PMID: 36161947; PMCID: PMC9546630. 8: Iida M, Nakane Y, Yoshimura T, Hirota T. Effects of cryptochrome-modulating compounds on circadian behavioural rhythms in zebrafish. J Biochem. 2022 May 11;171(5):501-507. doi: 10.1093/jb/mvab096. Erratum in: J Biochem. 2022 Mar 31;171(4):469. PMID: 34528676. 9: 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. 10: Miller S, Srivastava A, Nagai Y, Aikawa Y, Tama F, Hirota T. Structural differences in the FAD-binding pockets and lid loops of mammalian CRY1 and CRY2 for isoform-selective regulation. Proc Natl Acad Sci U S A. 2021 Jun 29;118(26):e2026191118. doi: 10.1073/pnas.2026191118. PMID: 34172584; PMCID: PMC8255803. 11: Zhou Y, Kreek MJ. Blockade of alcohol excessive and "relapse" drinking in male mice by pharmacological cryptochrome (CRY) activation. Psychopharmacology (Berl). 2021 Apr;238(4):1099-1109. doi: 10.1007/s00213-020-05757-9. Epub 2021 Jan 8. PMID: 33420591; PMCID: PMC7969462. 12: Buscone S, Mardaryev AN, Westgate GE, Uzunbajakava NE, Botchkareva NV. Cryptochrome 1 is modulated by blue light in human keratinocytes and exerts positive impact on human hair growth. Exp Dermatol. 2021 Feb;30(2):271-277. doi: 10.1111/exd.14231. Epub 2020 Nov 22. PMID: 33141439. 13: Liu W, An C, Shu X, Meng X, Yao Y, Zhang J, Chen F, Xiang H, Yang S, Gao X, Gao SS. A Dual-Plasmid CRISPR/Cas System for Mycotoxin Elimination in Polykaryotic Industrial Fungi. ACS Synth Biol. 2020 Aug 21;9(8):2087-2095. doi: 10.1021/acssynbio.0c00178. Epub 2020 Jul 16. Erratum in: ACS Synth Biol. 2022 May 20;11(5):1991. PMID: 32531165. 14: Alagha MA, Vágó J, Katona É, Takács R, van der Veen D, Zákány R, Matta C. A Synchronized Circadian Clock Enhances Early Chondrogenesis. Cartilage. 2021 Dec;13(2_suppl):53S-67S. doi: 10.1177/1947603520903425. Epub 2020 Feb 14. PMID: 32059614; PMCID: PMC8804825. 15: 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; PMCID: PMC7613259. 16: Abel JH, Chakrabarty A, Klerman EB, Doyle FJ 3rd. Pharmaceutical-based entrainment of circadian phase via nonlinear model predictive control. Automatica (Oxf). 2019 Feb;100:336-348. doi: 10.1016/j.automatica.2018.11.012. Epub 2018 Dec 10. PMID: 31673164; PMCID: PMC6822617. 17: Xue Y, Liu P, Wang H, Xiao C, Lin C, Liu J, Dong D, Fu T, Yang Y, Wang Z, Pan H, Chen J, Li Y, Cai D, Li Z. Modulation of Circadian Rhythms Affects Corneal Epithelium Renewal and Repair in Mice. Invest Ophthalmol Vis Sci. 2017 Mar 1;58(3):1865-1874. doi: 10.1167/iovs.16-21154. PMID: 28358954. 18: 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. PMID: 26174033; PMCID: PMC4576822. 19: 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. PMID: 25960183. 20: 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. PMID: 24449901; PMCID: PMC3918757.