ACLIDINIUM BROMIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H30NO4S2.Br
Molecular Weight	564.555
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Br-].OC(C(=O)O[C@H]1C[N+]3(CCCOC2=CC=CC=C2)CCC1CC3)(C4=CC=CS4)C5=CC=CS5

InChI

InChIKey=XLAKJQPTOJHYDR-QTQXQZBYSA-M

InChI=1S/C26H30NO4S2.BrH/c28-25(26(29,23-9-4-17-32-23)24-10-5-18-33-24)31-22-19-27(14-11-20(22)12-15-27)13-6-16-30-21-7-2-1-3-8-21;/h1-5,7-10,17-18,20,22,29H,6,11-16,19H2;1H/q+1;/p-1/t20?,22-,27?;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C26H29NO4S2
Molecular Weight	483.643
Charge	0
Count

Stereochemistry	EPIMERIC
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	BrH
Molecular Weight	80.912
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202450s006lbl.pdf
Curator's Comment: description was created based on several sources, including: | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002706/WC500132734.pdf | http://www.ncbi.nlm.nih.gov/pubmed/?term=24587893 | https://www.ncbi.nlm.nih.gov/pubmed/19710368

Aclidinium is a long-acting, competitive, and reversible anticholinergic drug that is specific for the acetylcholine muscarinic receptors. It binds to all 5 muscarinic receptor subtypes to a similar affinity. It has a much higher propensity to bind to muscarinic receptors than nicotinic receptors. FDA approved on July 24, 2012. Aclidinium's effects on the airways are mediated through the M3 receptor at the smooth muscle to cause bronchodilation. Prevention of acetylcholine-induced bronchoconstriction effects was dose-dependent and lasted longer than 24 hours.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002706/WC500132734.pdf	Antagonist 2778		0.14 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Bronchospasm associated with chronic obstructive pulmonary disease 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202450s006lbl.pdf	Secondary		Approved 8429	TUDORZA PRESSAIR Approved Use Indicated for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema Launch Date 2012

C_max

Value	Dose	Co-administered	Analyte	Population
194.2 pg/mL DRUG LABEL https://pubmed.ncbi.nlm.nih.gov/22366196/	400 μg single, oral dose: 400 μg route of administration: Oral experiment type: SINGLE co-administered:		ACLIDINIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
240.5 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22366196/	400 μg 2 times / day steady-state, oral dose: 400 μg route of administration: Oral experiment type: STEADY-STATE co-administered:		ACLIDINIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
386.7 pg × h/mL DRUG LABEL https://pubmed.ncbi.nlm.nih.gov/22366196/	400 μg single, oral dose: 400 μg route of administration: Oral experiment type: SINGLE co-administered:		ACLIDINIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
468.4 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22366196/	400 μg 2 times / day steady-state, oral dose: 400 μg route of administration: Oral experiment type: STEADY-STATE co-administered:		ACLIDINIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.9 h DRUG LABEL https://pubmed.ncbi.nlm.nih.gov/22366196/	400 μg single, oral dose: 400 μg route of administration: Oral experiment type: SINGLE co-administered:		ACLIDINIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22366196/	400 μg 2 times / day steady-state, oral dose: 400 μg route of administration: Oral experiment type: STEADY-STATE co-administered:		ACLIDINIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 ug single, intravenous Dose: 400 ug Route: intravenous Route: single Dose: 400 ug Sources: https://pubmed.ncbi.nlm.nih.gov/21628603	healthy, 30 years (range: 24-43 years) n = 6 Health Status: healthy Age Group: 30 years (range: 24-43 years) Sex: M Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/21628603	Sources: https://pubmed.ncbi.nlm.nih.gov/21628603
800 ug 2 times / day steady, respiratory Highest studied dose Dose: 800 ug, 2 times / day Route: respiratory Route: steady Dose: 800 ug, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/22366196	healthy, 39.3 years (range: 18-45 years) n = 8 Health Status: healthy Age Group: 39.3 years (range: 18-45 years) Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/22366196	Other AEs: Muscle spasm, Dysgeusia... Other AEs: Muscle spasm (12.5%) Dysgeusia (12.5%) Somnolence (12.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/22366196
6000 ug single, respiratory Highest studied dose Dose: 6000 ug Route: respiratory Route: single Dose: 6000 ug Sources: https://pubmed.ncbi.nlm.nih.gov/19640353/	healthy n = 16 Health Status: healthy Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/19640353/	Sources: https://pubmed.ncbi.nlm.nih.gov/19640353/
200 ug 2 times / day steady, respiratory Recommended Dose: 200 ug, 2 times / day Route: respiratory Route: steady Dose: 200 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000MedR.pdf Page: p. 101	unhealthy n = 891 Health Status: unhealthy Condition: COPD Population Size: 891 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000MedR.pdf Page: p. 101	Disc. AE: Non-cardiac chest pain, Headache... AEs leading to discontinuation/dose reduction: Non-cardiac chest pain (0.3%) Headache (0.2%) Dyspnea (0.2%) COPD (2%) Pruritus (0.2%) Syncope (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000MedR.pdf Page: p. 101
200 ug 2 times / day steady, respiratory Dose: 200 ug, 2 times / day Route: respiratory Route: steady Dose: 200 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000MedR.pdf Page: p. 101	unhealthy n = 448 Health Status: unhealthy Condition: COPD Population Size: 448 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000MedR.pdf Page: p. 101	Disc. AE: Fatigue, Non-cardiac chest pain... AEs leading to discontinuation/dose reduction: Fatigue (0.4%) Non-cardiac chest pain (0.2%) Dizziness (0.4%) Dyspnea (0.2%) COPD (2.9%) Pruritus (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000MedR.pdf Page: p. 101

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1767 inducer 389	inhibitor 1852 inducer 97	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278 CYP4A9/11 37 P-gp 1461	CYP450 65 P-gp 1537	CYP1A2 701 CYP2A6 79 CYP2B6 547 CYP2C8 168 CYP2C19 293 CYP2E1 128 CYP3A4/5 124 CYP4A9/11 2

Drug as perpetrator

Target	Modality	Activity
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	no [IC50 90 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	no
CYP2A6 739	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	no
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	no
CYP2D6 1891	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2E1 970	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	no
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP4A9/11 37	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP4A9/11 37	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=5 Page: 5.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000PharmR.pdf#page=156 Page: 156.0	yes [IC50 2.4 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000ClinPharmR.pdf#page=5 Page: 5.0	no
CYP450 65	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf#page=9 Page: 9.0	unlikely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202450Orig1s000PharmR.pdf#page=147 Page: 147.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:65346	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:65346
ZINC	ZINC000030691727	http://zinc15.docking.org/substances/ZINC000030691727

PubMed

Title	Date	PubMed
Inhalation by design: novel tertiary amine muscarinic M₃ receptor antagonists with slow off-rate binding kinetics for inhaled once-daily treatment of chronic obstructive pulmonary disease.	2011 Oct 13	21870878
Perampanel.	2013 Apr	24421482
Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases.	2014 Mar	24587893

Patents

Sample Use Guides

In Vivo Use Guide

One inhalation of TUDORZA PRESSAIR 400 mcg twice daily. For oral inhalation only.

Route of Administration: Other

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:54:09 GMT 2023` Edited by `admin` on `Fri Dec 15 15:54:09 GMT 2023`
Record UNII	UQW7UF9N91
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ACLIDINIUM BROMIDE

Official Name

English

(3R)-3-((2-HYDROXY-2,2-DI-2-THIENYLACETYL)OXY)-1-(3-PHENOXYPROPYL)-1-AZONIABICYCLO(2.2.2)OCTANE BROMIDE (1:1)

Systematic Name

English

1-AZONIABICYCLO(2.2.2)OCTANE, 3-((HYDROXYDI-2-THIENYLACETYL)OXY)-1-(3-PHENOXYPROPYL)-, BROMIDE, (3R)-

Systematic Name

English

1-AZONIABICYCLO(2.2.2)OCTANE, 3-((2-HYDROXY-2,2-DI-2-THIENYLACETYL)OXY)-1-(3-PHENOXYPROPYL)-, BROMIDE (1:1), (3R)-

Common Name

English

LAS-34273

Code

English

ACLIDINIUM BROMIDE [VANDF]

Common Name

English

Aclidinium Bromide [WHO-DD]

Common Name

English

TUDORZA PRESSAIR

Brand Name

English

aclidinium bromide [INN]

Common Name

English

LAS W-330

Code

English

LAS-34273 MICRONIZED

Code

English

ACLIDINIUM BROMIDE [ORANGE BOOK]

Common Name

English

DUAKLIR PRESSAIR COMPONENT ACLIDINIUM BROMIDE

Common Name

English

ACLIDINIUM BROMIDE [JAN]

Common Name

English

LAS34273

Code

English

ACLIDINIUM BROMIDE COMPONENT OF DUAKLIR PRESSAIR

Common Name

English

GENUAIR

Brand Name

English

ACLIDINIUM BROMIDE [MI]

Common Name

English

ACLIDINIUM BROMIDE [MART.]

Common Name

English

(3R)-3-{[Hydroxydi(thiophen-2-yl)acetyl]oxy}-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide

Systematic Name

English

ACLIDINIUM BROMIDE [USAN]

Common Name

English

LAS-W-330

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C29704