Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C29H34NO2 |
| Molecular Weight | 428.5858 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 1 |
SHOW SMILES / InChI
SMILES
OC(C1=CC=CC=C1)(C2=CC=CC=C2)C34CC[N+](CCOCC5=CC=CC=C5)(CC3)CC4
InChI
InChIKey=FVTWTVQXNAJTQP-UHFFFAOYSA-N
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
| Molecular Formula | C29H33NO2 |
| Molecular Weight | 427.5778 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/?term=19317446; http://www.ncbi.nlm.nih.gov/pubmed/?term=23435542;
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002751/WC500168425.pdf
Curator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/?term=19317446; http://www.ncbi.nlm.nih.gov/pubmed/?term=23435542;
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002751/WC500168425.pdf
Umeclidinium (used as a bromide salt) is a long-acting, antimuscarinic antagonist, often referred to as an anticholinergic, developed for the treatment of chronic obstructive pulmonary disease (COPD) (alone and in combination with Vilanterol - long-acting beta2-adrenergic agonist). Umeclidinium has similar affinity to the subtypes of muscarinic receptors M1 to M5 with Ki values of 0.16 nM, 0.15 nM, 0.06 nM, 0.05 nM and 0.13 nM for M1, M2, M3, M4 and M5, respectively. Umeclidinium is selective against mAChR over other unrelated receptors or channels such as κ and σ opiod receptors, Na+ channel and dopamine transporter. In the airways, it exhibits pharmacological effects through the inhibition of M3 receptor at the smooth muscle leading to bronchodilation. There is potential for an additive interaction with concomitantly used anticholinergic medicines.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P20309 Gene ID: 1131.0 Gene Symbol: CHRM3 Target Organism: Homo sapiens (Human) |
0.06 nM [Ki] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | ANORO ELLIPTA Approved UseIndicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Is NOT indicated for the relief of acute bronchospasm or for the treatment of asthma. Launch Date2013 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
995.9 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23284643/ |
500 μg single, oral dose: 500 μg route of administration: Oral experiment type: SINGLE co-administered: |
UMECLIDINIUM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
258 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25816315/ |
62.5 μg 1 times / day multiple, oral dose: 62.5 μg route of administration: Oral experiment type: MULTIPLE co-administered: |
UMECLIDINIUM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
245 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25816315/ |
62.5 μg 1 times / day multiple, oral dose: 62.5 μg route of administration: Oral experiment type: MULTIPLE co-administered: VILANTEROL |
UMECLIDINIUM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
575.7 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23284643/ |
500 μg single, oral dose: 500 μg route of administration: Oral experiment type: SINGLE co-administered: |
UMECLIDINIUM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
|
298 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25816315/ |
62.5 μg 1 times / day multiple, oral dose: 62.5 μg route of administration: Oral experiment type: MULTIPLE co-administered: |
UMECLIDINIUM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
304 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25816315/ |
62.5 μg 1 times / day multiple, oral dose: 62.5 μg route of administration: Oral experiment type: MULTIPLE co-administered: VILANTEROL |
UMECLIDINIUM plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.56 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23284643/ |
500 μg single, oral dose: 500 μg route of administration: Oral experiment type: SINGLE co-administered: |
UMECLIDINIUM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
125 ug 1 times / day steady, respiratory Dose: 125 ug, 1 times / day Route: respiratory Route: steady Dose: 125 ug, 1 times / day Sources: |
unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: |
Other AEs: Cough, Headache... Other AEs: Cough (14%) Sources: Headache (10%) Nasopharyngitis (7%) Upper respiratory tract infection (3%) Oropharyngeal pain (3%) |
250 ug 1 times / day steady, respiratory Highest studied dose Dose: 250 ug, 1 times / day Route: respiratory Route: steady Dose: 250 ug, 1 times / day Sources: |
unhealthy |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Headache | 10% | 125 ug 1 times / day steady, respiratory Dose: 125 ug, 1 times / day Route: respiratory Route: steady Dose: 125 ug, 1 times / day Sources: |
unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: |
| Cough | 14% | 125 ug 1 times / day steady, respiratory Dose: 125 ug, 1 times / day Route: respiratory Route: steady Dose: 125 ug, 1 times / day Sources: |
unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: |
| Oropharyngeal pain | 3% | 125 ug 1 times / day steady, respiratory Dose: 125 ug, 1 times / day Route: respiratory Route: steady Dose: 125 ug, 1 times / day Sources: |
unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: |
| Upper respiratory tract infection | 3% | 125 ug 1 times / day steady, respiratory Dose: 125 ug, 1 times / day Route: respiratory Route: steady Dose: 125 ug, 1 times / day Sources: |
unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: |
| Nasopharyngitis | 7% | 125 ug 1 times / day steady, respiratory Dose: 125 ug, 1 times / day Route: respiratory Route: steady Dose: 125 ug, 1 times / day Sources: |
unhealthy, 64.6 years Health Status: unhealthy Age Group: 64.6 years Sex: M+F Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205382Orig1s000ClinPharmR.pdf#page=58 Page: 58.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205382Orig1s000ClinPharmR.pdf#page=58 Page: 58.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205382Orig1s000ClinPharmR.pdf#page=58 Page: 58.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205382Orig1s000ClinPharmR.pdf#page=55 Page: 55.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205382Orig1s000ClinPharmR.pdf#page=58 Page: 58.0 |
yes [IC50 0.1 uM] | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205382Orig1s000ClinPharmR.pdf#page=58 Page: 58.0 |
yes [IC50 1 uM] |
Drug as victim
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203975Orig1s000PharmR.pdf#page=95 Page: 95.0 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| The combination of umeclidinium bromide and vilanterol in the management of chronic obstructive pulmonary disease: current evidence and future prospects. | 2013-12 |
|
| Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. | 2013-05 |
|
| Discovery of novel 1-azoniabicyclo[2.2.2]octane muscarinic acetylcholine receptor antagonists. | 2009-04-23 |
Sample Use Guides
ANORO ELLIPTA (umeclidinium/vilanterol 62.5 mcg/25 mcg) should be administered as 1 inhalation once daily by the orally inhaled route only. ANORO ELLIPTA should be taken at the same time every day. Do not use ANORO
ELLIPTA more than 1 time every 24 hours. No dosage adjustment is required for geriatric patients, patients with renal impairment, or patients with moderate hepatic impairment.
Route of Administration:
Respiratory
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=23435542
Using isolated human bronchial strips, umeclidinium was tested at concentrations from 1 nM to 100 nM ans showed potent inhibition of cells contraction. For these means segments of human bronchus were incubated with umeclidinium for 120 minutes prior to cumulative addition of carbachol in conventional tissue baths heated at 37°C.
| Substance Class |
Chemical
Created
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GE2T1418SV
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Validated (UNII)
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N0000175574
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C29704
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R03AL03
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GE2T1418SV
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1487514
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11519070
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DB09076
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C152796
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869185-19-3
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GE2T1418SV
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Umeclidinium
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DTXSID00235971
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CHEMBL1187833
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| Related Record | Type | Details | ||
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BINDER->LIGAND |
BINDING
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR |
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TRANSPORTER -> SUBSTRATE |
However, because of low oral bioavailability, inhibition of P-gp is unlikely to have an impact on the overall bioavailability of UMEC.
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT | |||
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ACTIVE MOIETY |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Biological Half-life | PHARMACOKINETIC |
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| Volume of Distribution | PHARMACOKINETIC |
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