Zatebradine HCl (UL-FS 49; UL-FS 49CL), the hydrochloride salt of Zatebradine, 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	C26H37CLN2O5
Molecular Weight	493.03538
Exact Mass	492.239
CAS #	91940-87-3
Related CAS #	Zatebradine;85175-67-3
PubChem CID	3045335
Appearance	Off-white to light yellow solid powder
Density	1.115g/cm3
Boiling Point	612.5ºC at 760mmHg
Flash Point	324.3ºC
LogP	3.952
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	11
Heavy Atom Count	34
Complexity	591
Defined Atom Stereocenter Count	0
InChi Key	ZRNKXJHEQKMWCH-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H36N2O5.ClH/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,6,9-14,18H2,1-5H31H
Chemical Name	3-[3-[2-(3,4-Dimethoxyphenyl)ethyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one hydrochloride
Synonyms	Zatebradine HCl UL-FS49 UL FS49Zatebradine Hydrochloride 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 Note: Please store this product in a sealed and protected environment, 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	In rabbit sinoatrial node cells, zatebradine exhibits an apparent Kd of 480 nM for usage-dependent inhibition of cardiac pacemaker currents [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.

Solubility Data

Solubility (In Vitro)

H2O : ~100 mg/mL (~202.82 mM) DMSO : ~100 mg/mL (~202.82 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.07 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 (5.07 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 (5.07 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. Solubility in Formulation 4: 110 mg/mL (223.11 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0282 mL	10.1412 mL	20.2823 mL
	5 mM	0.4056 mL	2.0282 mL	4.0565 mL
	10 mM	0.2028 mL	1.0141 mL	2.0282 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.