Umeclidinium
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Identification
- Summary
Umeclidinium is a long-acting muscarinic antagonist used as a long-term maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD).
- Brand Names
- Anoro, Anoro Ellipta, Incruse Ellipta, Trelegy Ellipta
- Generic Name
- Umeclidinium
- DrugBank Accession Number
- DB09076
- Background
Umeclidinium is a long-acting muscarinic antagonist (LAMA) used as a maintenance treatment for symptoms of chronic obstructive pulmonary disease (COPD). COPD is a progressive obstructive lung disease characterized by shortness of breath, cough, sputum production, and chronically poor airflow with a forced expiratory volume in 1 second (FEV1) of less than 80%.3
Maintenance of the airway is controlled by the parasympathetic nervous system, particularly by the abundance of the muscarinic subtype 3 (M3) in the airway smooth muscle.5 Parasympathetic ganglia are associated with the larger airways while postganglionic fibers innervate the smaller diameter bronchioles contributing to airway resistance.5 By blocking the M3 muscarinic receptor, umeclidinium inhibits the binding of acetylcholine and thereby opens up the airways by preventing bronchoconstriction.5 However, even though umeclidinium monotherapy is well-tolerated for up to 14 days, it is more likely to be used in combination therapy, as the international Gold Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommended the use of two long-acting bronchodilators with differing mechanisms of action to maximize efficacy and minimize adverse effects.4,2
Umeclidinium was approved by the FDA in April 2014 under the brand name Incruse Ellipta as a standalone product.14 Later, it was further approved as a combination product with vilanterol and vilanterol/fluticasone furoate under the brand name ANORO ELLIPTA and TRELEGY ELLIPTA respectively.9,10. ANORO ELLIPTA was approved in December 2013 while TRELEGY ELLIPTA was approved in September 2017.15,16
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 428.595
Monoisotopic: 428.258405759 - Chemical Formula
- C29H34NO2
- Synonyms
- 1-[2-(benzyloxy)ethyl]-4-[hydroxy(diphenyl)methyl]-1-azoniabicyclo[2.2.2]octane
- Umeclidinium
- External IDs
- GSK-573719
- GSK573719
- GSK573719A
Pharmacology
- Indication
Umeclidinium is approved by the FDA and Health Canada for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).7,8 Additionally, umeclidinium also exists as combination products with vilanterol or vilanterol and fluticasone furoate.9,10,12,13 Both products were indicated for the maintenance treatment of COPD, but only the umeclidinium/vilanterol/fluticasone furoate product was approved for the maintenance treatment of asthma in patients aged 18 years and older.9,10,12,13
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to manage Asthma Combination Product in combination with: Fluticasone furoate (DB08906), Vilanterol (DB09082) •••••••••••• •••••• Used in combination to manage Asthma Combination Product in combination with: Fluticasone furoate (DB08906), Vilanterol (DB09082) •••••••••••• •••••• Used in combination to manage Chronic obstructive pulmonary disease Combination Product in combination with: Vilanterol (DB09082), Fluticasone furoate (DB08906) •••••••••••• •••••• Used in combination to manage Chronic obstructive pulmonary disease Combination Product in combination with: Vilanterol (DB09082) •••••••••••• •••••• Used in combination to manage Chronic obstructive pulmonary disease Combination Product in combination with: Vilanterol (DB09082) •••••••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
QTc interval prolongation was studied in a double-blind, multiple-dose, placebo- and positive-controlled, crossover trial in 86 healthy subjects. Following repeat doses of umeclidinium 500 mcg once daily (8 times the recommended dosage) for 10 days, umeclidinium does not prolong QTc to any clinically relevant extent.7
In humans, the M3 receptor has been heavily implicated in the pathophysiology of asthma and COPD. Once the M3 receptor is activated, the phospholipase C would phosphorylate downstream targets, forming inositol 1,4,5-trisphosphate and eventually releasing intracellular Ca2+.6 Increase in intracellular Ca2+ results in muscle contraction, thus worsening COPD and asthma-related bronchoconstriction.6 Additionally, M3 receptor activation also regulates pathways involving CD38, cyclic ADP ribose (cADPR), and ryanodine receptor channels, all of which control the intracellular Ca2+ homeostasis that will lead to muscle contraction.6
- Mechanism of action
Umeclidinium is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of umeclidinium is predominantly a site-specific effect.7
Target Actions Organism AMuscarinic acetylcholine receptor M3 antagonistHumans UMuscarinic acetylcholine receptor M2 antagonistHumans UMuscarinic acetylcholine receptor M1 antagonistHumans UMuscarinic acetylcholine receptor M4 antagonistHumans UMuscarinic acetylcholine receptor M5 antagonistHumans - Absorption
Umeclidinium plasma levels may not predict therapeutic effect. Following inhaled administration of umeclidinium in healthy subjects, Cmax occurred at 5 to 15 minutes. Umeclidinium is mostly absorbed from the lung after inhaled doses with minimum contribution from oral absorption. Following repeat dosing of inhaled umeclidinium, steady state was achieved within 14 days with 1.8-fold accumulation.7 The absolute bioavailability of inhaled umeclidinium was on average 13% of the dose, with negligible contribution from oral absorption.8
- Volume of distribution
Following intravenous administration to healthy subjects, the mean volume of distribution was 86 L.7
- Protein binding
In vitro plasma protein binding in human plasma was on average 89%.7
- Metabolism
In vitro data showed that umeclidinium is primarily metabolized by the enzyme cytochrome P450 2D6 (CYP2D6) and is a substrate for the P-glycoprotein (P-gp) transporter. The primary metabolic routes for umeclidinium are oxidative (hydroxylation, O-dealkylation) followed by conjugation (e.g., glucuronidation), resulting in a range of metabolites with either reduced pharmacological activity or for which the pharmacological activity has not been established. Systemic exposure to the metabolites is low.7
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- Route of elimination
Following intravenous dosing with radiolabeled umeclidinium, mass balance showed 58% of the radiolabel in the feces and 22% in the urine. The excretion of the drug-related material in the feces following intravenous dosing indicated elimination in the bile. Following oral dosing to healthy male subjects, radiolabel recovered in feces was 92% of the total dose and that in urine was <1% of the total dose, suggesting negligible oral absorption.7
- Half-life
The effective half-life after once-daily inhaled dosing is 11 hours.7
- Clearance
Plasma clearance following intravenous administration was 151 L/hour.8
- Adverse Effects
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- Toxicity
In separate embryofetal developmental studies, pregnant rats and rabbits received umeclidinium during the period of organogenesis at doses up to approximately 50 and 200 times the maximum recommended human daily inhaled dose (MRHDID), respectively (on an AUC basis at maternal inhalation doses up to 278 mcg/kg/day in rats and at maternal subcutaneous doses up to 180 mcg/kg/day in rabbits). No evidence of teratogenic effects was observed in either species.7
In a perinatal and postnatal developmental study in rats, dams received umeclidinium during late gestation and lactation periods with no evidence of effects on offspring development at doses up to approximately 26 times the MRHDID (on an AUC basis at maternal subcutaneous doses up to 60 mcg/kg/day).7
Based on available data, no adjustment of the dosage of umeclidinium in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. Clinical trials of umeclidinium included 810 subjects aged 65 years and older, and, of those, 183 subjects were aged 75 years and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects.7
Umeclidinium produced no treatment-related increases in the incidence of tumors in 2-year inhalation studies in rats and mice at inhaled doses up to 137 and 295/200 mcg/kg/day (male/female), respectively (approximately 20 and 25/20 times the MRHDID in adults on an AUC basis, respectively).7
Umeclidinium tested negative in the following genotoxicity assays: the in vitro Ames assay, in vitro mouse lymphoma assay, and in vivo rat bone marrow micronucleus assay.7
No evidence of impairment of fertility was observed in male and female rats at subcutaneous doses up to 180 mcg/kg/day and at inhaled doses up to 294 mcg/kg/day, respectively (approximately 100 and 50 times, respectively, the MRHDID in adults on an AUC basis).7
No human overdosage data has been reported with umeclidinium High doses of umeclidinium may lead to anticholinergic signs and symptoms. However, there were no systemic anticholinergic adverse effects following a once-daily inhaled dose of up to 1,000 mcg of umeclidinium (16 times the maximum recommended daily dose) for 14 days in subjects with COPD. Treatment of overdosage consists of discontinuation of INCRUSE ELLIPTA together with institution of appropriate symptomatic and/or supportive therapy.7
In clinical trials, the most common adverse effects of umeclidinium were nasopharyngitis, upper respiratory tract infection, cough, and arthralgia. Atrial fibrillation occurred in <1% of patients, but was more common among patients treated with umeclidinium than in those treated with placebo. Anticholinergics like umeclidinium should be used with caution in patients with narrow-angle glaucoma and in those with prostatic hyperplasia or bladder-neck obstruction. Inhaled medications can cause paradoxical bronchospasm, which can be fatal.7
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The metabolism of Umeclidinium can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Umeclidinium. Abiraterone The metabolism of Umeclidinium can be decreased when combined with Abiraterone. Abrocitinib The serum concentration of Umeclidinium can be increased when it is combined with Abrocitinib. Acebutolol The metabolism of Umeclidinium can be decreased when combined with Acebutolol. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Umeclidinium bromide 7AN603V4JV 869113-09-7 PEJHHXHHNGORMP-UHFFFAOYSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Incruse Ellipta Powder, metered 55 mcg Respiratory (inhalation) Glaxosmithkline Inc 2016-09-08 Not applicable EU Incruse Ellipta Powder 62.5 mcg / act Respiratory (inhalation) Glaxosmithkline Inc 2015-04-27 Not applicable Canada Incruse Ellipta Powder, metered 55 mcg Respiratory (inhalation) Glaxosmithkline Inc 2016-09-08 Not applicable EU Incruse Ellipta Aerosol, powder 62.5 ug/1 Oral Glaxosmithkline Inc 2014-04-30 Not applicable US Incruse Ellipta Powder, metered 55 mcg Respiratory (inhalation) Glaxosmithkline Inc 2016-09-08 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Anoro Umeclidinium bromide (55 micrograms) + Vilanterol trifenatate (22 micrograms) Powder, metered Respiratory (inhalation) Glaxosmithkline Inc 2016-09-08 Not applicable EU Anoro Umeclidinium bromide (55 micrograms) + Vilanterol trifenatate (22 micrograms) Powder, metered Respiratory (inhalation) Glaxosmithkline Inc 2016-09-08 Not applicable EU Anoro Umeclidinium bromide (55 micrograms) + Vilanterol trifenatate (22 micrograms) Powder, metered Respiratory (inhalation) Glaxosmithkline Inc 2016-09-08 Not applicable EU Anoro Ellipta Umeclidinium bromide (62.5 ug/1) + Vilanterol trifenatate (25 ug/1) Powder Respiratory (inhalation) Glaxosmithkline Inc 2014-01-31 Not applicable US ANORO ELLIPTA Umeclidinium (55 µg) + Vilanterol (22 µg) Powder Respiratory (inhalation) Glaxosmithkline Inc 2014-10-03 Not applicable Italy
Categories
- ATC Codes
- R03AL08 — Vilanterol, umeclidinium bromide and fluticasone furoate
- R03AL — Adrenergics in combination with anticholinergics incl. triple combinations with corticosteroids
- R03A — ADRENERGICS, INHALANTS
- R03 — DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
- R — RESPIRATORY SYSTEM
- R03AL — Adrenergics in combination with anticholinergics incl. triple combinations with corticosteroids
- R03A — ADRENERGICS, INHALANTS
- R03 — DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
- R — RESPIRATORY SYSTEM
- Drug Categories
- Adrenergics, Inhalants
- Agents producing tachycardia
- Agents to Treat Airway Disease
- Anticholinergic Agents
- Antimuscarinics Antispasmodics
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 Substrates
- Drugs for Obstructive Airway Diseases
- Muscarinic Antagonists
- OCT1 substrates
- OCT2 Substrates
- P-glycoprotein substrates
- Pulmonary Disease, Chronic Obstructive, drug therapy
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylmethanes
- Direct Parent
- Diphenylmethanes
- Alternative Parents
- Benzylethers / Quinuclidines / Aralkylamines / Piperidines / Tetraalkylammonium salts / Tertiary alcohols / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organic salts show 3 more
- Substituents
- Alcohol / Amine / Aralkylamine / Aromatic alcohol / Aromatic heteropolycyclic compound / Azacycle / Benzylether / Dialkyl ether / Diphenylmethane / Ether show 14 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- GE2T1418SV
- CAS number
- 869185-19-3
- InChI Key
- FVTWTVQXNAJTQP-UHFFFAOYSA-N
- InChI
- InChI=1S/C29H34NO2/c31-29(26-12-6-2-7-13-26,27-14-8-3-9-15-27)28-16-19-30(20-17-28,21-18-28)22-23-32-24-25-10-4-1-5-11-25/h1-15,31H,16-24H2/q+1
- IUPAC Name
- 1-[2-(benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-azabicyclo[2.2.2]octan-1-ium
- SMILES
- OC(C1=CC=CC=C1)(C1=CC=CC=C1)C12CC[N+](CCOCC3=CC=CC=C3)(CC1)CC2
References
- General References
- Feldman GJ, Edin A: The combination of umeclidinium bromide and vilanterol in the management of chronic obstructive pulmonary disease: current evidence and future prospects. Ther Adv Respir Dis. 2013 Dec;7(6):311-9. doi: 10.1177/1753465813499789. Epub 2013 Sep 3. [Article]
- Decramer M, Maltais F, Feldman G, Brooks J, Harris S, Mehta R, Crater G: Bronchodilation of umeclidinium, a new long-acting muscarinic antagonist, in COPD patients. Respir Physiol Neurobiol. 2013 Jan 15;185(2):393-9. doi: 10.1016/j.resp.2012.08.022. Epub 2012 Sep 28. [Article]
- Tal-Singer R, Cahn A, Mehta R, Preece A, Crater G, Kelleher D, Pouliquen IJ: Initial assessment of single and repeat doses of inhaled umeclidinium in patients with chronic obstructive pulmonary disease: two randomised studies. Eur J Pharmacol. 2013 Feb 15;701(1-3):40-8. doi: 10.1016/j.ejphar.2012.12.019. Epub 2012 Dec 28. [Article]
- Scott LJ, Hair P: Umeclidinium/Vilanterol: first global approval. Drugs. 2014 Mar;74(3):389-95. doi: 10.1007/s40265-014-0186-8. [Article]
- Salmon M, Luttmann MA, Foley JJ, Buckley PT, Schmidt DB, Burman M, Webb EF, DeHaas CJ, Kotzer CJ, Barrett VJ, Slack RJ, Sarau HM, Palovich MR, Laine DI, Hay DW, Rumsey WL: Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70. doi: 10.1124/jpet.112.202051. Epub 2013 Feb 22. [Article]
- Gosens R, Zaagsma J, Meurs H, Halayko AJ: Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res. 2006 May 9;7(1):73. doi: 10.1186/1465-9921-7-73. [Article]
- FDA Approved Drug Products: INCRUSE ELLIPTA (umeclidinium inhalation powder) for oral inhalation use [Link]
- Health Canada Approved Drug Proucts: INCRUSE ELLIPTA (umeclidinium dry powder) for oral inhalation [Link]
- FDA Approved Drug Products: ANORO ELLIPTA (umeclidinium and vilanterol inhalation powder) for oral inhalation use [Link]
- FDA Approved Drug Products: Trelegy Ellipta (fluticasone furoate, umeclidinium, and vilanterol) powder for inhalation (December 2022) [Link]
- CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW: Umeclidinium Bromide [Link]
- Health Canada Approved Drug Proucts: ANORO ELLIPTA (umeclidinium/vilanterol powder) for oral inhalation [Link]
- Health Canada Approved Drug Proucts: TRELEGY ELLIPTA (fluticasone furoate/umeclidinium/vilanterol powder) for oral inhalation [Link]
- GSK receives approval for Incruse™ Ellipta® (umeclidinium) in the US for the treatment of COPD [Link]
- FDA approves Anoro Ellipta to treat chronic obstructive pulmonary disease [Link]
- FDA approves Trelegy Ellipta as the first once-daily single inhaler triple therapy for the treatment of both asthma and COPD in the US [Link]
- FDA Approved Drug Products: Trelegy Ellipta (fluticasone furoate, umeclidinium, and vilanterol) powder for inhalation (June 2023) [Link]
- FDA Approved Drug Products: INCRUSE ELLIPTA (umeclidinium inhalation powder), for oral inhalation use (Jan 2024) [Link]
- External Links
- KEGG Drug
- D10180
- PubChem Compound
- 11519070
- PubChem Substance
- 347827824
- ChemSpider
- 9693858
- BindingDB
- 50267614
- 1487514
- ChEBI
- 79041
- ChEMBL
- CHEMBL1187833
- ZINC
- ZINC000034608502
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Umeclidinium_bromide
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Chronic Obstructive Pulmonary Disease (COPD) 4 somestatus stop reason just information to hide 4 Completed Basic Science Chronic Obstructive Pulmonary Disease (COPD) 1 somestatus stop reason just information to hide 4 Completed Treatment Chronic Obstructive Pulmonary Disease (COPD) 4 somestatus stop reason just information to hide 4 Not Yet Recruiting Prevention Chronic Obstructive Pulmonary Disease (COPD) 1 somestatus stop reason just information to hide 4 Recruiting Prevention Chronic Obstructive Pulmonary Disease (COPD) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Powder Buccal Aerosol, powder Respiratory (inhalation) Powder, metered Respiratory (inhalation) 62.5 mcg Powder Oral; Respiratory (inhalation) 55 mcg Tablet Oral 62.5 mg Powder Buccal 74.200 mcg Aerosol, powder Oral 62.5 ug/1 Powder Respiratory (inhalation) 62.5 mcg / act Powder Respiratory (inhalation) 62.5 mcg/1blister Powder, metered Respiratory (inhalation) 55 MCG Aerosol, powder Respiratory (inhalation) 62.5 mg Powder, metered Respiratory (inhalation) 62.5 mcg Powder Respiratory (inhalation) 55 mcg Aerosol, powder Respiratory (inhalation) 55 mcg Powder Respiratory (inhalation) Powder, metered Respiratory (inhalation) - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5873360 Yes 1999-02-23 2016-08-23 US US7101866 No 2006-09-05 2021-08-03 US US7439393 Yes 2008-10-21 2025-11-21 US US6759398 No 2004-07-06 2021-08-03 US USRE44874 No 2014-04-29 2023-03-23 US US6537983 No 2003-03-25 2021-08-03 US US8511304 Yes 2013-08-20 2027-12-14 US US7629335 No 2009-12-08 2021-08-03 US US8161968 Yes 2012-04-24 2028-08-05 US US8746242 Yes 2014-06-10 2031-04-11 US US8113199 Yes 2012-02-14 2028-04-23 US US7776895 No 2010-08-17 2022-09-11 US US8534281 Yes 2013-09-17 2030-09-08 US US6878698 No 2005-04-12 2021-08-03 US US8309572 No 2012-11-13 2025-04-27 US US8183257 No 2012-05-22 2025-07-27 US US7488827 No 2009-02-10 2025-04-27 US US7498440 No 2009-03-03 2025-04-27 US US8201556 No 2012-06-19 2029-02-05 US US9333310 Yes 2016-05-10 2028-04-02 US US9750726 No 2017-09-05 2030-11-29 US US9750762 No 2017-09-05 2030-11-29 US US11090294 No 2021-08-17 2030-11-29 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 1.94e-05 mg/mL ALOGPS logP 2.88 ALOGPS logP 0.68 Chemaxon logS -7.4 ALOGPS pKa (Strongest Acidic) 13.04 Chemaxon pKa (Strongest Basic) -3.7 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 29.46 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 141.75 m3·mol-1 Chemaxon Polarizability 50.42 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-000x-6696000000-9b62f23b3d6560b76225 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 191.803 predictedDeepCCS 1.0 (2019) [M+H]+ 194.19856 predictedDeepCCS 1.0 (2019) [M+Na]+ 200.1111 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- acetylcholine binding
- Gene Name
- CHRM3
- Uniprot ID
- P20309
- Uniprot Name
- Muscarinic acetylcholine receptor M3
- Molecular Weight
- 66127.445 Da
References
- Salmon M, Luttmann MA, Foley JJ, Buckley PT, Schmidt DB, Burman M, Webb EF, DeHaas CJ, Kotzer CJ, Barrett VJ, Slack RJ, Sarau HM, Palovich MR, Laine DI, Hay DW, Rumsey WL: Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70. doi: 10.1124/jpet.112.202051. Epub 2013 Feb 22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol
- Specific Function
- arrestin family protein binding
- Gene Name
- CHRM2
- Uniprot ID
- P08172
- Uniprot Name
- Muscarinic acetylcholine receptor M2
- Molecular Weight
- 51714.605 Da
References
- Salmon M, Luttmann MA, Foley JJ, Buckley PT, Schmidt DB, Burman M, Webb EF, DeHaas CJ, Kotzer CJ, Barrett VJ, Slack RJ, Sarau HM, Palovich MR, Laine DI, Hay DW, Rumsey WL: Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70. doi: 10.1124/jpet.112.202051. Epub 2013 Feb 22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- CHRM1
- Uniprot ID
- P11229
- Uniprot Name
- Muscarinic acetylcholine receptor M1
- Molecular Weight
- 51420.375 Da
References
- Salmon M, Luttmann MA, Foley JJ, Buckley PT, Schmidt DB, Burman M, Webb EF, DeHaas CJ, Kotzer CJ, Barrett VJ, Slack RJ, Sarau HM, Palovich MR, Laine DI, Hay DW, Rumsey WL: Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70. doi: 10.1124/jpet.112.202051. Epub 2013 Feb 22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- CHRM4
- Uniprot ID
- P08173
- Uniprot Name
- Muscarinic acetylcholine receptor M4
- Molecular Weight
- 53048.65 Da
References
- Salmon M, Luttmann MA, Foley JJ, Buckley PT, Schmidt DB, Burman M, Webb EF, DeHaas CJ, Kotzer CJ, Barrett VJ, Slack RJ, Sarau HM, Palovich MR, Laine DI, Hay DW, Rumsey WL: Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70. doi: 10.1124/jpet.112.202051. Epub 2013 Feb 22. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- CHRM5
- Uniprot ID
- P08912
- Uniprot Name
- Muscarinic acetylcholine receptor M5
- Molecular Weight
- 60073.205 Da
References
- Salmon M, Luttmann MA, Foley JJ, Buckley PT, Schmidt DB, Burman M, Webb EF, DeHaas CJ, Kotzer CJ, Barrett VJ, Slack RJ, Sarau HM, Palovich MR, Laine DI, Hay DW, Rumsey WL: Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70. doi: 10.1124/jpet.112.202051. Epub 2013 Feb 22. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Feldman GJ, Edin A: The combination of umeclidinium bromide and vilanterol in the management of chronic obstructive pulmonary disease: current evidence and future prospects. Ther Adv Respir Dis. 2013 Dec;7(6):311-9. doi: 10.1177/1753465813499789. Epub 2013 Sep 3. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW: Umeclidinium Bromide [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW: Umeclidinium Bromide [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Feldman GJ, Edin A: The combination of umeclidinium bromide and vilanterol in the management of chronic obstructive pulmonary disease: current evidence and future prospects. Ther Adv Respir Dis. 2013 Dec;7(6):311-9. doi: 10.1177/1753465813499789. Epub 2013 Sep 3. [Article]
- FDA Approved Drug Products: INCRUSE ELLIPTA (umeclidinium inhalation powder) for oral inhalation use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- Negligible at clinical doses
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
- Specific Function
- (R)-carnitine transmembrane transporter activity
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW: Umeclidinium Bromide [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- Negligible at clinical doses
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- acetylcholine transmembrane transporter activity
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW: Umeclidinium Bromide [Link]
Drug created at May 19, 2015 16:00 / Updated at November 03, 2024 19:35