KL001 is a first-in-class cryptochrome protein (CRY, a blue light-sensitive flavoprotein involved in regulating circadian rhythms in animals and plants) stabilizer that specifically interacts with CRY1 and CRY2. KL001 prevents ubiquitin-dependent CRY degradation, thereby extending the circadian cycle. KL001 may be used to control fasting hormone-induced gluconeogenesis.

Physicochemical Properties

Molecular Formula	C21H22N2O4S
Molecular Weight	398.477
Exact Mass	398.13
Elemental Analysis	C, 63.30; H, 5.57; N, 7.03; O, 16.06; S, 8.05
CAS #	309928-48-1
PubChem CID	2888648
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	578.1±60.0 °C at 760 mmHg
Flash Point	303.4±32.9 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.642
LogP	4.7
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Heavy Atom Count	28
Complexity	600
Defined Atom Stereocenter Count	0
SMILES	S(C([H])([H])[H])(N(C([H])([H])C1=C([H])C([H])=C([H])O1)C([H])([H])C([H])(C([H])([H])N1C2=C([H])C([H])=C([H])C([H])=C2C2=C([H])C([H])=C([H])C([H])=C12)O[H])(=O)=O
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
Chemical Name	N-(3-carbazol-9-yl-2-hydroxypropyl)-N-(furan-2-ylmethyl)methanesulfonamide
Synonyms	KL 001; KL-001; KL001
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	KL001 (0.03-71 μM) induces a controlled circadian manner, resulting in a longer period and smaller amplitude of circadian rhythms in stable U2OS reporter cell lines expressing Bmal1-dLuc or Per2-dLuc [1). Without altering their basal expression in primary mouse hepatocytes, KL001 (2-8 μM; 18 hours) inhibits the glucagon-dependent induction of Pck1 and G6pc genes [1].
References	[1]. Identification of small molecule activators of cryptochrome. Science. 2012 Aug 31;337(6098):1094-7. [2]. Circadian molecular clocks and cancer. Cancer Lett. 2014 Jan 1;342(1):9-18. [3]. Crystal structure of mammalian cryptochrome in complex with a small molecule competitor of its ubiquitin ligase. Cell Res. 2013 Dec;23(12):1417-9.

Solubility Data

Solubility (In Vitro)

DMSO : ~5 mg/mL (~12.55 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (3.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (3.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1.25 mg/mL (3.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5095 mL	12.5477 mL	25.0954 mL
	5 mM	0.5019 mL	2.5095 mL	5.0191 mL
	10 mM	0.2510 mL	1.2548 mL	2.5095 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.