Nebivolol HCl (R 065824)

Alias: Silostar; Bystolic; R 67145; R-67145; R67145; Nebivolol HCl; Nebivolol Hydrochloride

Cat No.:V26343 Purity: ≥98%

COA Product Data Instructions for use SDS

Nebivolol (also known as R-65824) potently and selectively inhibits β1-adrenoceptor with IC50 of 0.8 NM.

Nebivolol HCl (R 065824) Chemical Structure CAS No.: 152520-56-4
Product category: Adrenergic Receptor

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Nebivolol HCl (R 065824):

Nebivolol (R 065824)

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Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Nebivolol (also known as R-65824) potently and selectively inhibits β1-adrenoceptor with IC50 of 0.8 NM. Nebivolol demonstrates high selectivity and affinity for beta 1-adrenergic receptor sites in a lung membrane preparation from a rabbit (beta 2/beta 1 ratio = 50 and Ki value = 0.9 nM). With a Ki(β2)/Ki(β1) value of 40.7, which competition experiments judge to be 3H-CGP 12.1777 in the presence of CGP 207.12 A (300 nM, Kiβ2) or ICI 118.551 (50 nM, Kiβ1), Nebivolol exhibits β1-adrenoceptor selectivity.

Biological Activity I Assay Protocols (From Reference)

Targets	β1-adrenoceptor ( IC50 = 0.8 nM )
ln Vitro	Nebivolol demonstrates high affinity and selectivity for beta 1-adrenergic receptor sites in a rabbit lung membrane preparation (Ki value = 0.9 nM and beta 2/beta 1 ratio = 50).[1] Nebivolol demonstrates selectivity for β1-adrenoceptors with a Ki(β2)/Ki(β1) value of 40.7, as determined by competition experiments to 3H-CGP 12.1777 when CGP 207.12 A (300 nM, Kiβ2) or ICI 118.551 (50 nM, Kiβ1) are present.[2] Nebivolol inhibits human endothelial cells (haECs) and coronary smooth muscle cells (haCSMCs) in a manner that is concentration- and time-dependent. After 7 days of treatment, a significant reduction in the cell growth of haCSMCs is observed with an IC50 of 6.1 μM. Additionally, the accelerated proliferation of haCSMCs stimulated by growth factors TGFβ, bFGF, and PDGF-BB is inhibited with IC50 values of 6.8 μM, 6.4 μM, and 7.7 μM, respectively. After giving haCSMCs a 10-to 5-microgram dose of nibevolol for 48 hours, 23% of the cells undergo moderate apoptosis, and the proportion of S-phase cells falls from 16% to 5%. HaCEs produce more NO during Nebivolol incubation, but endothelin-1 transcription and secretion are inhibited.[3]
ln Vivo	Nebivolol administration reduces myocardial apoptosis in rats with myocardial infarction (MI). This effect is mediated by regulation of NO and occurs first by intravenous injection within 10 minutes of reperfusion and then orally. Nebivolol decreases both total and localized apoptotic cardiomyocytes and considerably prevents variations in left ventricular (LV) pressure. Treatment with nevivolol slightly but not significantly lowers the mean blood pressure (MBP) in rats suffering from MI.[4]
Cell Assay	Nebivolol (10^-7~10^-5 M) is added to cells at varying concentrations for 1, 2, 4, 7, and 14 days. Bromodeoxyuridine (BrdU) incorporation is used to analyze cell proliferation, while PI or annexin V staining is used to identify cell apoptosis.
Animal Protocol	Male Sprague Dawley rat myocardial infarction (MI) model 2.0 mg/kg Gastric gavage once daily
References	[1]. Mol Pharmacol . 1988 Dec;34(6):843-51. [2]. Br J Pharmacol . 2001 Aug;133(8):1330-8. [3]. Cardiovasc Res . 2001 Feb 1;49(2):430-9. [4]. Circ J . 2008 Apr;72(4):660-70.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C22H26CLF2NO4
Molecular Weight	441.8960
Exact Mass	441.15
Elemental Analysis	C, 59.80; H, 5.93; Cl, 8.02; F, 8.60; N, 3.17; O, 14.48
CAS #	152520-56-4
Related CAS #	Nebivolol; 118457-14-0
Appearance	Solid powder
SMILES	C1CC2=C(C=CC(=C2)F)O[C@H]1[C@H](CNC[C@@H]([C@@H]3CCC4=C(O3)C=CC(=C4)F)O)O.Cl
InChi Key	JWEXHQAEWHKGCW-BIISKSHESA-N
InChi Code	InChI=1S/C22H25F2NO4.ClH/c23-15-3-7-19-13(9-15)1-5-21(28-19)17(26)11-25-12-18(27)22-6-2-14-10-16(24)4-8-20(14)29-22;/h3-4,7-10,17-18,21-22,25-27H,1-2,5-6,11-12H2;1H/t17-,18-,21-,22+;/m0./s1
Chemical Name	(1S)-1-[(2S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-[[(2S)-2-[(2R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl]amino]ethanol;hydrochloride
Synonyms	Silostar; Bystolic; R 67145; R-67145; R67145; Nebivolol HCl; Nebivolol Hydrochloride
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)

Solubility Data

Solubility (In Vitro)	DMSO: 88~100 mg/mL (199.1~226.3 mM)
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 2.08 mg/mL (4.71 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 20.8 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: ≥ 2.08 mg/mL (4.71 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 20.8 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. View More Solubility in Formulation 3: ≥ 2.08 mg/mL (4.71 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 5% DMSO + 20% PEG300 + 5%Tween 80 + 70%ddH2O: 4.4mg/ml (9.96mM) (Please use freshly prepared in vivo formulations for optimal results.)

Solubility (In Vitro)

DMSO: 88~100 mg/mL (199.1~226.3 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.71 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 20.8 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: ≥ 2.08 mg/mL (4.71 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 20.8 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.

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (4.71 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 4: 5% DMSO + 20% PEG300 + 5%Tween 80 + 70%ddH2O: 4.4mg/ml (9.96mM)

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2630 mL	11.3148 mL	22.6296 mL
	5 mM	0.4526 mL	2.2630 mL	4.5259 mL
	10 mM	0.2263 mL	1.1315 mL	2.2630 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.

Calculator

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
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See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
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The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05328310	Active Recruiting	Drug: Nebivolol	Hypertension	Korea University Anam Hospital	January 6, 2019	Not Applicable
NCT05728632	Active Recruiting	Drug: Nebivolol Drug: Placebo	Breast Cancer Cardiotoxicity	Giulio Stefanini	January 1, 2019	Phase 3
NCT06104423	Recruiting	Drug: Nebivolol 5 mg Drug: Ramipril 2.5/5/10 mg	Hypertension	Menarini International Operations Luxembourg SA	October 2, 2023	Phase 4
NCT06035978	Not yet recruiting	Drug: Nebivolol Drug: Carvedilol	Cardiovascular Diseases Heart Failure With Reduced Ejection Fraction	University Hospital Ostrava	March 2024	Phase 4
NCT03778554	Recruiting	Drug: Nebivolol Drug: Carvedilol Drug: Nebivolol	Acute Myocardial Infarction ST Elevation Myocardial Infarction	Bispebjerg Hospital	December 17, 2018	Phase 4

Biological Data

Rank order of β1-adrenoceptor selectivity of nebivolol, bisoprolol, metoprolol, bucindolol and carvedilol. Br J Pharmacol . 2001 Aug;133(8):1330-8.

Percentage changes of isoprenaline pre-stimulated force of contraction obtained in human left ventricular failing myocardium after application of metoprolol, carvedilol and nebivolol. Br J Pharmacol . 2001 Aug;133(8):1330-8.

Influence of bucindolol and nebivolol on adenylate cyclase activity in crude membrane preparations of human left ventricular non-failing myocardium. Br J Pharmacol . 2001 Aug;133(8):1330-8.