Zatebradine (UL-FS-49; UL-FS-49CL) is a novel and potent bradycardic agent which inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channels with an IC50 values 1.96 µM. . It blocks hyperpolarization-activated inward current (If) through cyclic nucleotide-gated cation (HCN) channels in sinoatrial node cells.

Physicochemical Properties

Molecular Formula	C26H36N2O5
Molecular Weight	456.574447631836
Exact Mass	456.262
CAS #	85175-67-3
Related CAS #	Zatebradine hydrochloride;91940-87-3
PubChem CID	65637
Appearance	Light yellow to yellow solid powder
Density	1.115g/cm3
Boiling Point	612.5ºC at 760 mmHg
Flash Point	324.3ºC
Index of Refraction	1.545
LogP	3.6
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	11
Heavy Atom Count	33
Complexity	591
Defined Atom Stereocenter Count	0
SMILES	O=C1CC2C(=CC(=C(C=2)OC)OC)CCN1CCCN(CCC1C=C(OC)C(OC)=CC=1)C
InChi Key	KEDQCFRVSHYKLR-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H36N2O5/c1-27(13-9-19-7-8-22(30-2)23(15-19)31-3)11-6-12-28-14-10-20-16-24(32-4)25(33-5)17-21(20)18-26(28)29/h7-8,15-17H,6,9-14,18H2,1-5H3
Chemical Name	3-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one
Synonyms	UL-FS-49 free base UL-FS-49CL free baseUL-FS49 UL FS49 ULFS49
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
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	When it comes to usage-dependently blocking cardiac pacemaker currents from rabbit sinoatrial node cells, zebradine has an apparent Kd of 480 nM [2].
ln Vivo	Zatebradine (0–20 mg/kg; intraperitoneally; 30 min; male C57/Bl6 mice) increased cardiac arrhythmias and dose-dependently decreased heart rate from 600 to 200 bpm (ED50 = 1.8 mg/kg) [1].
Animal Protocol	Animal/Disease Models: Male C57/Bl6-mouse[1] Doses: 0mg/kg, 0.1mg/kg, 1mg/kg, 10mg/kg, 20mg/kg Route of Administration: intraperitoneal (ip) injection; 30 minutes Experimental Results: Acute blood glucose was observed diminished, dose-dependent reductions in glycated hemoglobin Dramatically prevented the reduction in IRI levels at the 3 and 10 mg/kg doses, with no differences in food intake or body weight.
References	[1]. Bradycardic and proarrhythmic properties of sinus node inhibitors. Mol Pharmacol. 2006 Apr;69(4):1328-37. Epub 2005 Dec 30. [2]. Use-dependent blockade of cardiac pacemaker current (If) by cilobradine and zatebradine. Eur J Pharmacol. 2003 Oct 8;478(2-3):161-71.
Additional Infomation	3-[3-[2-(3,4-dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one is a benzazepine.

Solubility Data

Solubility (In Vitro)

Ethanol : ~100 mg/mL (~219.02 mM) DMSO : ≥ 50 mg/mL (~109.51 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.48 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 25.0 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: ≥ 2.5 mg/mL (5.48 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), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (5.48 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 25.0 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	2.1902 mL	10.9512 mL	21.9024 mL
	5 mM	0.4380 mL	2.1902 mL	4.3805 mL
	10 mM	0.2190 mL	1.0951 mL	2.1902 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.