| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
AD109 targets specific neurological pathways in the hypoglossal motor nucleus that control upper airway dilator muscles. Atomoxetine, a norepinephrine reuptake inhibitor, increases noradrenergic tone to enhance genioglossus muscle activity. Aroxybutynin, a novel antimuscarinic, blocks cholinergic signaling that contributes to muscle relaxation during REM sleep. The combination synergistically activates the hypoglossal motor nucleus to increase signals to the upper airway during sleep, preventing collapse in OSA patients. This dual mechanism targets the neuromuscular root cause of airway obstruction.
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| ln Vitro |
In preclinical studies and clinical trials, AD109 has demonstrated significant activity in reducing OSA severity. In a Phase 3 trial (SynAIRgy, n=646 adults with mild-to-severe OSA), AD109 treatment resulted in a mean reduction from baseline in apnea-hypopnea index (AHI) of 46.8% at 26 weeks, compared to 6.8% with placebo. The drug improves oxygenation during sleep and targets the underlying cause of airway collapse, representing the first oral pharmacologic therapy for OSA.
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| ln Vivo |
In a Phase 3 clinical trial (SynAIRgy), AD109 demonstrated robust efficacy in reducing OSA severity. At 26 weeks, the active treatment group showed a mean AHI reduction of 46.8% from baseline, while the placebo group showed only a 6.8% reduction. AD109 also improves the daytime consequences of OSA, such as fatigue. The LunAIRo and SynAIRgy Phase 3 trials have been fully enrolled to confirm and extend the understanding of AD109's efficacy and safety in OSA with longer-term use.
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| Enzyme Assay |
Not applicable. AD109 is a combination drug product evaluated in clinical trials. For non-cellular receptor binding assays, individual components can be tested: atomoxetine binds to the norepinephrine transporter (NET) with high affinity, while aroxybutynin binds to muscarinic acetylcholine receptors (M1-M5). A standard radioligand binding assay uses membrane preparations from cells expressing recombinant human NET or muscarinic receptors, incubated with 3H-labeled ligands and varying concentrations of each compound to calculate Ki values.
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| Cell Assay |
Not applicable. AD109 is not tested in routine cell-based assays as a combination. However, the individual components have established cellular pharmacology: atomoxetine (0.1-10 uM) inhibits norepinephrine uptake in cells expressing NET (IC50 ~5 nM). Aroxybutynin (0.1-100 nM) antagonizes carbachol-induced calcium mobilization in CHO cells expressing M3 receptors. These assays involve loading cells with Fluo-4 AM and measuring fluorescence. DMSO vehicle control (≤0.1%). Positive controls: desipramine (NET), atropine (muscarinic).
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| Animal Protocol |
For in vivo efficacy, AD109 has been evaluated in Phase 3 clinical trials (LunAIRo, SynAIRgy). In the SynAIRgy trial, 646 adults with mild-to-severe OSA who were intolerant to or refused positive airway pressure (PAP) therapy were randomized to AD109 or placebo once nightly at bedtime for 6 months. Primary endpoint: change in AHI from baseline at week 26. Secondary endpoints: oxygen desaturation index, Epworth Sleepiness Scale score, and functional outcomes of sleep. AD109 demonstrated a significant reduction in AHI (46.8% vs 6.8% for placebo).
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| ADME/Pharmacokinetics |
AD109 is an oral drug with favorable pharmacokinetics for once-daily bedtime administration. Atomoxetine has an oral bioavailability of ~60-80%, Tmax of 1-2 h, and terminal half-life (t½) of 3-6 h. Aroxybutynin is rapidly absorbed and extensively metabolized; its active metabolite (desethylaroxybutynin) contributes to its antimuscarinic effect. Coadministration with GLP-1 RAs does not cause large differences in PK. Food may affect absorption; however, the bedtime dosing regimen minimizes this effect. For storage, powder at -20degC for up to 3 years.
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| Toxicity/Toxicokinetics |
In Phase 3 trials, AD109 was generally well-tolerated, with a manageable safety profile. The most common treatment-emergent adverse events (TEAEs) were dry mouth, decreased appetite, nausea, and constipation, reported with higher incidence in the AD109 arm. Most AEs were mild to moderate in severity. However, tolerability remains a challenge, with some early discontinuations due to side effects. No serious or unexpected safety signals were reported. Standard laboratory safety precautions should be followed; for research use only.
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| References | |
| Additional Infomation |
AD109 is an investigational oral drug for obstructive sleep apnea. It consists of atomoxetine (a selective norepinephrine reuptake inhibitor) and aroxybutynin (a novel antimuscarinic agent). The combination has received FDA Fast Track designation. Two Phase 3 trials (LunAIRo, SynAIRgy) have been completed. Molecular formula of combination: not applicable; each component has its own formula. For research use only; not for human therapy outside clinical trials.
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| Molecular Formula |
C39H52N2O4
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|---|---|
| Molecular Weight |
612.84
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| Appearance |
Typically exists as solids at room temperature
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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 | 1.6317 mL | 8.1587 mL | 16.3175 mL | |
| 5 mM | 0.3263 mL | 1.6317 mL | 3.2635 mL | |
| 10 mM | 0.1632 mL | 0.8159 mL | 1.6317 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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