Salmeterol Xinafoate (GR-33343G, AHR-3929; AH-3923; Salmetedur, Serevent), the Xinafoate salt of Salmeterol, is a potent and long-acting β2-adrenergic receptor agonist with anti-inflammatory effects. It binds to the WT β2-adrenergic receptor and activates it at a Ki of 1.5 nM. Salmeterol is primarily used to treat chronic obstructive pulmonary disease, or COPD, and asthma. Breathlessness, wheezing, coughing, and tightness in the chest are some of these symptoms. Salmeterol is also used to avoid exercise-induced bronchospasm, a condition that causes breathing difficulties.

Physicochemical Properties

Molecular Formula	C36H45NO7
Molecular Weight	603.75
Exact Mass	603.319
Elemental Analysis	C, 71.62; H, 7.51; N, 2.32; O, 18.55
CAS #	94749-08-3
Related CAS #	Salmeterol; 89365-50-4; Salmeterol-d3 xinafoate; Salmeterol-13C6 xinafoate
PubChem CID	56801
Appearance	White to off-white solid powder
Density	1.112g/cm3
Boiling Point	603ºC at 760 mmHg
Melting Point	137-138ºC
Flash Point	318.5ºC
Index of Refraction	1.565
LogP	6.741
Hydrogen Bond Donor Count	6
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	17
Heavy Atom Count	44
Complexity	629
Defined Atom Stereocenter Count	0
SMILES	O=C(C1C(O)=C2C(C=CC=C2)=CC=1)O.OC1C(CO)=CC(C(CNCCCCCCOCCCCC2C=CC=CC=2)O)=CC=1
InChi Key	XTZNCVSCVHTPAI-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H37NO4.C11H8O3/c27-20-23-18-22(13-14-24(23)28)25(29)19-26-15-7-1-2-8-16-30-17-9-6-12-21-10-4-3-5-11-21;12-10-8-4-2-1-3-7(8)5-6-9(10)11(13)14/h3-5,10-11,13-14,18,25-29H,1-2,6-9,12,15-17,19-20H2;1-6,12H,(H,13,14)
Chemical Name	2-(hydroxymethyl)-4-[1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]ethyl]phenol;1-hydroxynaphthalene-2-carboxylic acid
Synonyms	AHR 3929; AHR-3929; AH-3923; AH3923; Salmeterol xinafoate; GR-33343G; AHR3929; AH 3923; GR-33343X xinafoate; GR 33343X xinafoate; Salmetedur, Serevent®
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

Targets	β2 adrenoceptor ( pEC50 = 9.6 ); β1 adrenoceptor ( pEC50 = 6.1 ); β3 adrenoceptor ( pEC50 = 5.9 )
ln Vitro	In vitro activity: Salmeterol (0.001-25 µM) suppresses the proliferation of human T cells[2].
ln Vivo	Salmeterol (0.16 mg/kg), formoterol (0.32 mg/kg), and their combination therapy have therapeutic effects in mice with chronic obstructive pulmonary disease (COPD)[3].
Enzyme Assay	After twice being rinsed with ice-cold phosphate-buffered saline, the cells are mechanically detached in an ice-cold buffer that contains 10 mM Tris·HCl, pH 7.4, 5 mM EDTA, 10 μg/mL benzamidine, 10 μg/mL soybean trypsin inhibitor (type II-S), and 5 μg/mL leupeptin (lysis buffer). 10 minutes at 4°C are spent centrifuging the lysate at 45,000 ×g. Using a Potter-xstyle homogenizer, the pellet is rehomogenized in lysis buffer and kept at -80°C until needed. The competition binding assays are run for 60 minutes at 37°C with 1–5 μg of membrane protein, 50 pM 125I–CYP, and 0-100 μM unlabeled ligand in the presence of 100 μM GTP in a buffer containing 75 mM Tris·HCl, pH 7.4, 12.5 mM MgCl2, and 2 mM EDTA. Whatman GF/C filters are quickly diluted and rapidly filtered through them to stop the binding reaction. The filters are then three times washed with a solution containing 25 mM Tris·HCl, pH 7.4, and 1 mM MgCl2. Nonspecific binding is assessed when 5 μM (±)-propranolol is present. Using a γ-counter, the radioactivity on the filters is measured.
Cell Assay	Salmeterol dramatically reduces RAW264.7 and THP-1 cells' ability to produce pro-inflammatory mediators. Salmeterol inhibits phosphorylation of ERK1/2 and JNK by PgLPS, but not p38 MAP kinases (MAP-K). Moreover, salmeterol inhibits p65-NFκB's nuclear translocation, NF-κB transcriptional activity, and IκBα phosphorylation to lessen NF-κB activation. Salmeterol exhibits extremely high selectivity with a Ki of 1.5±0.4 nM for the WT β2AR (β1 Ki /β2 Ki ratio of roughly 1500). Salmeterol inhibits IRS-1Ser307 phosphorylation levels brought on by tumor necrosis factor-α. In retinal Müller cells, salmeterol alone inhibits cell death (p<0.05 compared to 25 mM glucose). When combined with IRS-1shRNA, salmeterol significantly increases cell death as compared to when used alone. Furthermore, treatment with salmeterol alone dramatically lowers cytochrome C levels; however, this effect is mitigated when salmeterol is coupled with IRS-1 shRNA. At 10 μM, salmeterol has no effect on the differentiation and maturation of DCs; instead, it induces apoptosis in DCs. Salmeterol (10 μM) inhibits the activation of MAPK and NF-κB and reduces the mRNA and protein levels of pro-inflammatory cytokines in LPS-activated DCs.
Animal Protocol	Male C57BL/6 mice (6-8 weeks old, body weight: 32-35 g) Salmeterol (0.16 mg/kg) and/or Formoterol (0.32 mg/kg) The therapeutic efficacy of co-treatment was investigated in this model over a 56-day-long observation period.
References	[1]. PThe discovery of long-acting saligenin β₂ adrenergic receptor agonists incorporating a urea group. Bioorg Med Chem. 2011 Oct 15;19(20):6026-32. [2]. Effects of beta2-agonists on resident and infiltrating inflammatory cells. J Allergy Clin Immunol. 2002 Dec;110(6 Suppl):S282-90. [3]. Efficacy of salmeterol and formoterol combination treatment in mice with chronic obstructive pulmonary disease. Exp Ther Med. 2018 Feb;15(2):1538-1545.
Additional Infomation	Salmeterol xinafoate is a naphthoic acid. A selective ADRENERGIC BETA-2 RECEPTOR agonist that functions as a BRONCHODILATOR when administered by inhalation. It is used to manage the symptoms of ASTHMA and CHRONIC OBSTRUCTIVE PULMONARY DISEASE. See also: Salmeterol (has active moiety); Fluticasone propionate; salmeterol xinafoate (component of).

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~165.6 mM) Water: <1 mg/mL Ethanol: ~4 mg/mL (~6.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.45 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 (3.45 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.45 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 + Corn oil: 5.0mg/ml (8.28mM)  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6563 mL	8.2816 mL	16.5631 mL
	5 mM	0.3313 mL	1.6563 mL	3.3126 mL
	10 mM	0.1656 mL	0.8282 mL	1.6563 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.