INDACATEROL MALEATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H28N2O3.C4H4O4
Molecular Weight	508.5629
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

OC(=O)\C=C/C(O)=O.CCC1=CC2=C(CC(C2)NC[C@H](O)C3=CC=C(O)C4=C3C=CC(=O)N4)C=C1CC

InChI

InChIKey=IREJFXIHXRZFER-PCBAQXHCSA-N

InChI=1S/C24H28N2O3.C4H4O4/c1-3-14-9-16-11-18(12-17(16)10-15(14)4-2)25-13-22(28)19-5-7-21(27)24-20(19)6-8-23(29)26-24;5-3(6)1-2-4(7)8/h5-10,18,22,25,27-28H,3-4,11-13H2,1-2H3,(H,26,29);1-2H,(H,5,6)(H,7,8)/b;2-1-/t22-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	C24H28N2O3
Molecular Weight	392.4907
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

Indacaterol is an ultra-long-acting beta-adrenoceptor agonist developed by Novartis. It was approved by the European Medicines Agency (EMA) under the trade name Onbrez Breezhaler on November 30, 2009, and by the United States Food and Drug Administration (FDA), under the trade name Arcapta Neohaler, on July 1, 2011. It needs to be taken only once a day, unlike the related drugs formoterol and salmeterol. It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD) (long-term data in patients with asthma are thus far lacking). It is delivered as an aerosol formulation through a dry powder inhaler.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Beta-2 adrenergic receptor 203	Agonist 2,678	76.0 nM [Ki]
Beta-1 adrenergic receptor 158	Agonist 2,678	91.4 nM [Ki]
Beta-2 adrenergic receptor 203	Agonist 2,678	76.0 nM [Ki]
Beta-1 adrenergic receptor 158	Agonist 2,678	91.4 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), 4	Primary		Approved 8,429	ARCAPTA NEOHALER
Airflow obstruction in patients with chronic obstructive pulmonary disease (COPD) 4	Primary		Approved 8,429	ARCAPTA

C_max

Value	Dose	Co-administered	Analyte	Population
528 pg/mL	110 μg 1 times / day steady-state, respiratory	GLYCOPYRROLATE	INDACATEROL plasma	Homo sapiens
339 pg/mL	110 μg single, respiratory	GLYCOPYRROLATE	INDACATEROL plasma	Homo sapiens
0.206 ng/mL	150 μg single, respiratory		INDACATEROL serum	Homo sapiens
0.518 ng/mL	300 μg single, respiratory		INDACATEROL serum	Homo sapiens
0.299 ng/mL	150 μg 1 times / day steady-state, respiratory		INDACATEROL serum	Homo sapiens
0.697 ng/mL	300 μg 1 times / day steady-state, respiratory		INDACATEROL serum	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
2750 pg × h/mL	110 μg 1 times / day steady-state, respiratory	GLYCOPYRROLATE	INDACATEROL plasma	Homo sapiens
907 pg × h/mL	110 μg single, respiratory	GLYCOPYRROLATE	INDACATEROL plasma	Homo sapiens
0.974 ng × h/mL	150 μg single, respiratory		INDACATEROL serum	Homo sapiens
2.43 ng × h/mL	300 μg single, respiratory		INDACATEROL serum	Homo sapiens
2.51 ng × h/mL	150 μg 1 times / day steady-state, respiratory		INDACATEROL serum	Homo sapiens
6.52 ng × h/mL	300 μg 1 times / day steady-state, respiratory		INDACATEROL serum	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
116 h	150 μg 1 times / day steady-state, respiratory		INDACATEROL serum	Homo sapiens
118 h	300 μg 1 times / day steady-state, respiratory		INDACATEROL serum	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
800 ug 1 times / day multiple, respiratory Highest studied dose	unhealthy, 43.5 years (range: 12.0–64.0 years) n = 59	Disc. AE: Dyspnea, Wheezing...
75 ug 1 times / day multiple, respiratory	unhealthy	Other AEs: Adverse event...

Showing 1 to 2 of 2 entries

Previous1Next

AEs

Show entries

AE	Significance	Dose	Population
Asthma	moderate, 1 patient Disc. AE	800 ug 1 times / day multiple, respiratory Highest studied dose	unhealthy, 43.5 years (range: 12.0–64.0 years) n = 59
Cough	moderate, 1 patient Disc. AE	800 ug 1 times / day multiple, respiratory Highest studied dose	unhealthy, 43.5 years (range: 12.0–64.0 years) n = 59
Dyspnea	serious, 1 patient Disc. AE	800 ug 1 times / day multiple, respiratory Highest studied dose	unhealthy, 43.5 years (range: 12.0–64.0 years) n = 59
Wheezing	serious, 1 patient Disc. AE	800 ug 1 times / day multiple, respiratory Highest studied dose	unhealthy, 43.5 years (range: 12.0–64.0 years) n = 59
Adverse event	grade 5	75 ug 1 times / day multiple, respiratory	unhealthy

Showing 1 to 5 of 5 entries

Previous1Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737	substrate 1,037 inhibitor 1,767	substrate 1,217 inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2E1 882 CYP3A4/5 278 CYP1A2 1,524 CYP2C8 911 CYP2C19 1,478 P-gp 1,461 MRP2 383 BCRP 699 hOCT1 10	UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A8 283 UGT1A9 380 UGT1A10 291 UGT2B7 389 UGT2B15 203 CYP1A1 349 CYP1A2 1,054 CYP1B1 92 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C18 138 CYP2C19 991 CYP2E1 667 CYP3A5 395 CYP4A11 119 P-gp 1,537	P-gp 257 MRP2 111

Drug as perpetrator

Show entries

Target	Modality	Activity
MRP2 475	inducer 1,573	negligible
P-gp 1,650	inducer 1,573	negligible
CYP2C9 1,819	inhibitor 3,277	no
CYP2E1 970	inhibitor 3,277	no
CYP3A4/5 335	inhibitor 3,277	no

Showing 1 to 5 of 13 entries

Previous1 2 3Next

Drug as victim

Show entries

Target	Modality	Activity
CYP3A5 395	substrate 3,367	likely
CYP1A1 349	substrate 3,367	low
CYP2D6 1,217	substrate 3,367	low
CYP1A2 1,054	substrate 3,367	no
CYP1B1 92	substrate 3,367	no

Showing 1 to 5 of 24 entries

Previous1 2 3 4 5Next

Tox targets

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

Showing 1 to 1 of 1 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:68575	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:68575
ChemicalBook	CB72566367	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB72566367
ChemicalBook	CB82512068	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB82512068
MolPort	MolPort-023-219-171	https://www.molport.com/shop/molecule-link/MolPort-023-219-171
ZINC	ZINC000035801098	http://zinc15.docking.org/substances/ZINC000035801098

Showing 1 to 5 of 5 entries

Previous1Next

PubMed

Show entries

Title	Date	PubMed
Gateways to clinical trials.	2006 Jan-Feb	16541195
Indacaterol Novartis/skyePharma.	2006 May	16729723
ultra-long-acting beta2-adrenoceptor agonists: an emerging therapeutic option for asthma and COPD?	2007	17352511
Gateways to clinical trials.	2007 Jan-Feb	17344945
Efficacy and safety of indacaterol, a new 24-hour beta2-agonist, in patients with asthma: a dose-ranging study.	2008 Dec	19085578

Showing 1 to 5 of 18 entries

Previous1 2 3 4Next

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage of Indacaterol is the once-daily inhalation of the contents of one 75 mcg Indacaterol capsule using the NEOHALER inhaler.

Route of Administration: Respiratory

In Vitro Use Guide

In the isolated tracheal strip preparation, indacaterol, demonstrated concentration-dependent inhibition of electrically induced contraction (EC50= 45 ± 13 nM)