Formoterol fumarate dihydrate (also known as Foradil) is a long-acting β2 agonist (LABA) used in the treatment of asthma and COPD (chronic obstructive pulmonary disease). It is marketed in three forms: a dry-powder inhaler, a metered-dose inhaler and an inhalation solution, under various trade names including Atock, Atimos/Atimos Modulite, Foradil/Foradile, Oxeze/Oxis, and Perforomist. Mometasone/formoterol and Budesonide/formoterol combination formulations are also available for purchase. Unlike salbutamol (albuterol), which acts for 4 to 6 hours, formoterol acts for up to 12 hours. This is a longer duration of action than other short-acting β2 agonists. In addition to prophylactic corticosteroid therapy, LABAs like formoterol are used as "symptom controllers." When treating acute asthma, LABAs are not advised; instead, a "reliever" short-acting β2 agonist (such as salbutamol) is still needed.

Physicochemical Properties

Molecular Formula	2(C19H24N2O4).C4H4O4.2(H2O)
Molecular Weight	496.51
Exact Mass	840.379
CAS #	183814-30-4
Related CAS #	Formoterol fumarate; 43229-80-7
PubChem CID	60196271
Appearance	White to off-white solid powder
Boiling Point	603.2ºC at 760 mmHg
Melting Point	116-120ºC
Flash Point	318.6ºC
Vapour Pressure	2.12E-15mmHg at 25°C
LogP	6.229
Hydrogen Bond Donor Count	12
Hydrogen Bond Acceptor Count	16
Rotatable Bond Count	18
Heavy Atom Count	60
Complexity	507
Defined Atom Stereocenter Count	4
SMILES	C[C@H](NC[C@@H](O)C1=CC(NC=O)=C(O)C=C1)CC2=CC=C(OC)C=C2.C[C@H](NC[C@@H](O)C1=CC(NC=O)=C(O)C=C1)CC2=CC=C(OC)C=C2.O=C(O)/C=C/C(O)=O.O.O
InChi Key	RATSWNOMCHFQGJ-XODSYJLDSA-N
InChi Code	InChI=1S/2C19H24N2O4.C4H4O4.2H2O/c2*1-13(9-14-3-6-16(25-2)7-4-14)20-11-19(24)15-5-8-18(23)17(10-15)21-12-22;5-3(6)1-2-4(7)8;;/h2*3-8,10,12-13,19-20,23-24H,9,11H2,1-2H3,(H,21,22);1-2H,(H,5,6)(H,7,8);2*1H2/b;;2-1+;;
Chemical Name	(E)-but-2-enedioic acid;N-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethyl]phenyl]formamide;dihydrate
Synonyms	(-)-Formoterol; Arformoterol; (R,R)-Formoterol; Formoterol; arformoterol; (R,R)-Formoterol; BD 40A; eformoterol; Foradil; formoterol fumarate; Trade names: Atock; Atimos/Atimos Modulite; Foradil/Foradile; Oxeze/Oxis; Perforomist
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	In vitro activity: Formoterol inhibited the phosphorylation of JNK1 and GR-Ser226, which restored Dex sensitivity. Partially inhibiting H(2) O(2)-induced PI3Kδ-dependent (PKB) phosphorylation was formoterol (FM), but not SM. H(2) O(2) lowered the amount of cAMP produced in U937 cells by SM, but had no discernible impact on the cells' reaction to FM.
ln Vivo	Formoterol exposure for 24 or 72 hours increased the number of copies of mtDNA in the kidney and heart, increased the number of copies of peroxisome proliferator-activated receptor γ coactivator 1α, and increased the number of genes involved in the mitochondrial electron transport chain (F0 subunit 6 of transmembrane F-type ATP synthase, NADH dehydrogenase subunit 1, NADH dehydrogenase subunit 6, and NADH dehydrogenase [ubiquinone] 1β subcomplex subunit 8). Rat uterine contraction amplitude and frequency were inhibited by formoterol and ritodrine, with IC50 values of 3.8 x 10(-10) and 4.7 x 10(-7) M, respectively.
Enzyme Assay	Formoterol((also known as arformoterol) exhibits great potential as a β2-agonist that may provide desired metabolic effects with its unique and highly β2-selective adrenergic agonist properties.
Animal Protocol	Mouse
References	[1]. Am J Respir Cell Mol Biol. 2011 Jul; 45(1): 88–94. Published online 2010 Sep 20. [2]. BMC Pediatr . 2012 Mar 7:12:21.
Additional Infomation	Formoterol Fumarate is the fumarate salt form of formoterol, a long-acting and selective sympathomimetic beta-receptor agonist with bronchodilator activity. Formoterol fumarate binds beta 2 adrenergic receptors in bronchial smooth muscle and stimulates intracellular adenyl cyclase, thereby increasing the production of cyclic adenosine monophosphate (cAMP). Increased cAMP levels cause relaxation of bronchial smooth muscle, improve mucociliary clearance and reduce mediator substance release in inflammatory cells, especially from mast cells. (NCI05) An ADRENERGIC BETA-2 RECEPTOR AGONIST with a prolonged duration of action. It is used to manage ASTHMA and in the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. See also: Formoterol Fumarate (annotation moved to).

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 50 mg/mL Water: < 1 mg/mL Ethanol: N/A

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0141 mL	10.0703 mL	20.1406 mL
	5 mM	0.4028 mL	2.0141 mL	4.0281 mL
	10 mM	0.2014 mL	1.0070 mL	2.0141 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.