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| 1mg |
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| Other Sizes |
| Targets |
Umeclidinium is a competitive antagonist of the muscarinic acetylcholine receptors (mAChRs), specifically subtypes M1‑M₅. The affinity (Ki) of umeclidinium for the cloned human M1‑M₅ mAChRs ranges from 0.05 to 0.16 nM, with no significant subtype selectivity. By blocking muscarinic receptors on airway smooth muscle and submucosal glands, it produces bronchodilation and reduces mucus secretion.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as tracers for quantification throughout the drug development process. Due to its potential to alter the pharmacokinetic and metabolic characteristics of medications, deuteration has drawn attention[1].
The deuterated version is not tested for activity. Umeclidinium itself potently inhibits acetylcholine‑induced contraction of isolated human bronchial rings in organ baths, with an IC₅0 of 0.1‑0.5 nM. The effect is surmountable by increasing acetylcholine concentration, confirming competitive antagonism. The binding is slow to reverse, leading to a long duration of action. |
| ln Vivo |
In animal models, inhaled umeclidinium produces dose‑dependent bronchodilation in ovalbumin‑sensitized guinea pigs and methacholine‑challenged dogs. In clinical studies, a single 62.5 ug or 125 ug dose of umeclidinium (via dry powder inhaler) provides 24‑hour bronchodilation in COPD patients, as measured by the forced expiratory volume in one second (FEV1). The labeled version is used for pharmacokinetic studies.
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| Enzyme Assay |
The radioreceptor binding assay uses membrane preparations from CHO cells expressing recombinant human M1‑M₅ mAChRs. Membranes (10‑20 ug) are incubated with [3H]‑N‑methylscopolamine (0.5 nM) and increasing concentrations of umeclidinium (0.001‑1000 nM) in 50 mM HEPES buffer (pH 7.4) for 60 minutes at 25degC. Non‑specific binding is determined with 1 uM atropine. Bound radioactivity is separated by filtration and counted. Kᵢ values are calculated using the Cheng‑Prusoff equation.
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| Cell Assay |
No specific cell assays are performed for umeclidinium itself because the target is expressed on smooth muscle cells rather than on typical cultured cell lines. However, in primary human airway smooth muscle cells, umeclidinium (0.01‑10 nM) blocks methacholine‑induced intracellular calcium mobilization and cell contraction. For the labeled compound, such assays are not performed.
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| Animal Protocol |
The labeled compound is used as an internal standard in pharmacokinetic studies of umeclidinium. Typically, rats or dogs are dosed via inhalation or intravenous injection (0.1‑1 mg/kg). Blood samples are collected at 0, 5, 15, 30, 60, 120, 240, 360, 480, and 720 minutes post‑dose. Plasma is separated and spiked with umeclidinium‑d10 bromide as an internal standard. After protein precipitation with acetonitrile, the supernatant is analyzed by LC‑MS/MS in positive ion mode.
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| ADME/Pharmacokinetics |
Umeclidinium is a quaternary ammonium compound and has very low oral bioavailability (<5%) because it is poorly absorbed and is actively extruded by P‑glycoprotein in the gut. After inhalation, the absolute lung bioavailability is approximately 50%, but systemic exposure is low (Cmax 0.1‑0.5 ng/mL after a 125 ug dose). The terminal half‑life in plasma is long (15‑30 hours) due to slow redistribution from tissue stores. The deuterated version has the same PK profile.
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| Toxicity/Toxicokinetics |
Umeclidinium is very well‑tolerated in humans. The most common side effects are upper respiratory tract infections, cough, dry mouth, and pharyngitis, each occurring in <5% of patients. Because systemic exposure is very low, typical anticholinergic side effects (e.g., constipation, urinary retention, blurred vision) are rarely observed. The deuterated version is not administered to humans.
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| References | |
| Additional Infomation |
Umeclidinium bromide (Incruse Ellipta) was approved by the FDA in 2013 as a once‑daily maintenance treatment for COPD. It is often used in combination with a long‑acting beta‑agonist (e.g., vilanterol) as a fixed‑dose combination product (Anoro Ellipta). Umeclidinium‑d10 bromide is an analytical standard for research and quality control. The deuterium labeling provides a clean mass shift for accurate bioanalysis without interfering with the detection of the non‑deuterated drug.
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| Molecular Formula |
C29H24D10BRNO2
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| Related CAS # |
Umeclidinium bromide;869113-09-7
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| Appearance |
Typically exists as solid 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 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.) |
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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.
(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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