| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
Description: Navafenterol saccharinate (AZD-8871) is a novel and potent inhaled long-acting dual-pharmacology muscarinic antagonist/β 2 -adrenoceptor agonist (MABA) in development for the treatment of obstructive airways diseases. The safety, tolerability, pharmacodynamics, and pharmacokinetics of navafenterol were investigated in patients with mild asthma.
| ln Vitro |
Navafenterol (AZD-8871) has pIC50 values of 9.9, 9.9, 9.5, 10.4, and 8.8 for human M1, M2, M3, M4, and M5 receptors, respectively[1]. Navafenterol's pEC50 values for β1, β2, and β3 adrenergic receptors are 9.0, 9.5, and 8.7, in that order. Compared to β1 and β3 subtypes (three-fold and six-fold, respectively), it is more selective for β2 adrenergic receptors [1]. When compared to M2 receptors, navafenterol shows kinetic selectivity for M3 receptors (half-life: 4.97 hours) (half-life: 0.46 hours) [1]. In isolated guinea pig tissues, navafenterol demonstrated dual antimuscarinic and β2-adrenoceptor functional activity (pIC50 in electrically stimulated trachea: 8.6; pEC50 in self-sounding isolated trachea: 8.8) and over time. There is still a transition[1].
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| ln Vivo |
In dogs and guinea pigs, navafenterol (AZD-8871) inhibits acetylcholine-induced bronchoconstriction and, at doses with bronchoprotective efficacy, has negligible effects on heart rate and salivation. Moreover, dogs who received AZD8871 had long-lasting benefits, with a bronchial protective half-life of more than 24 hours. With an ID40 of 0.40 µg/kg, navafenterol demonstrated dose-proportionate bronchial protection without a discernible potency difference [1].
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| Animal Protocol |
Animal/Disease Models: Male Dunkin Hartley guinea pig (body weight 340-600 g) bronchoconstriction model [1]
Doses: 10, 30, 100 and 300 μg/mL Route of Administration: Aerosol administration Experimental Results: Concentration-response inhibition of bronchoconstriction, The IC50 value is 2.1 µg/mL. Exhibits anti-sialic acid effects, with a maximum inhibition rate of 65% ± 11% on salivation at a concentration of 300 µg/mL, with an estimated IC50 of 138.4 µg/mL. Animal/Disease Models: Male anesthetized beagle dog [1] Doses: 0.3, 1, 3 or 10 µg/kg Route of Administration: Administered as a nebulized liquid aerosol; administration volume 3 mL Experimental Results: At all doses tested (0.3-10 µg/kg) demonstrated significant effects within 24 hrs (hrs (hours)). The dose of 10 µg/kg demonstrated long-lasting effects, with bronchial protection of 79% ± 3.6% at 24 hrs (hrs (hours)) and a calculated half-life longer than 24 hrs (hrs (hours)). |
| References |
[1]. Mònica Aparici, et al. Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M3 Receptor Antagonist/ β 2-Adrenoceptor Agonist Molecule with Long-Lasting Effects and Favorable Safety Profile. J Pharmacol Exp Ther. 2019 Jul;370(1):127-136.
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| Molecular Weight |
926.091186761856
|
|---|---|
| Exact Mass |
925.259
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| CAS # |
1648550-37-1
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| Related CAS # |
Navafenterol;1435519-06-4
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| PubChem CID |
90467467
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
64
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| Complexity |
1530
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S1C=CC=C1C(C1=CC=CS1)(C(=O)OC1CCC(CC1)N(C)CCCN1C2C=CC(CNC[C@@H](C3=CC=C(C4=C3C=CC(N4)=O)O)O)=CC=2N=N1)O.S1(C2C=CC=CC=2C(N1)=O)(=O)=O
|
| InChi Key |
WXFYZNXSBYPTSS-KYWULLABSA-N
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| InChi Code |
1S/C38H42N6O6S2.C7H5NO3S/c1-43(25-8-10-26(11-9-25)50-37(48)38(49,33-5-2-19-51-33)34-6-3-20-52-34)17-4-18-44-30-14-7-24(21-29(30)41-42-44)22-39-23-32(46)27-12-15-31(45)36-28(27)13-16-35(47)40-369-7-5-3-1-2-4-6(5)12(10,11)8-7/h2-3,5-7,12-16,19-21,25-26,32,39,45-46,49H,4,8-11,17-18,22-23H2,1H3,(H,40,47)1-4H,(H,8,9)/t25-,26-,32-/m0./s1
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| Chemical Name |
(1r,4r)-4-((3-(5-((((R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-1H-benzo[d][1,2,3]triazol-1-yl)propyl)(methyl)amino)cyclohexyl 2-hydroxy-2,2-di(thiophen-2-yl)acetate compound with benzo[d]isothiazol-3(2H)-one 1,1-dioxide (1
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| Synonyms |
AZD-8871 saccharinate, AZD8871 saccharinate, LAS-191351 saccharinate, LAS191351 saccharinate
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0798 mL | 5.3990 mL | 10.7981 mL | |
| 5 mM | 0.2160 mL | 1.0798 mL | 2.1596 mL | |
| 10 mM | 0.1080 mL | 0.5399 mL | 1.0798 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.
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.
(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.
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