OLODATEROL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H26N2O5
Molecular Weight	386.4415
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(CC(C)(C)NC[C@H](O)C2=CC(O)=CC3=C2OCC(=O)N3)C=C1

InChI

InChIKey=COUYJEVMBVSIHV-SFHVURJKSA-N

InChI=1S/C21H26N2O5/c1-21(2,10-13-4-6-15(27-3)7-5-13)22-11-18(25)16-8-14(24)9-17-20(16)28-12-19(26)23-17/h4-9,18,22,24-25H,10-12H2,1-3H3,(H,23,26)/t18-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.drugdevelopment-technology.com/projects/striverdi-respimat-for-the-maintenance-treatment-of-copd/; http://www.ncbi.nlm.nih.gov/pubmed/?term=20371707

Olodaterol is a beta2-adrenoceptor agonist discovered by Boehringer Ingelheim and approved for the treatment of Chronic Obstructive Pulmonary Disease. The compound exerts its pharmacological effects by binding and activation of beta2-adrenoceptors after inhalation. Activation of these receptors in the airways results in a stimulation of intracellular adenyl cyclase, an enzyme that mediates the synthesis of cyclic-3’, 5’ adenosine monophosphate (cAMP). Elevated levels of cAMP induce bronchodilation by relaxation of airway smooth muscle cells. Olodaterol effect lasts for 24 hours.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-2 adrenergic receptor 203 Target ID: P07550\|\|\|Q53GA6\|\|\|Q9UCZ3 Gene ID: 154.0 Gene Symbol: ADRB2 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=20371707	Agonist 2678		0.1 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic obstructive pulmonary disease 174 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf	Primary		Approved 8429	STRIVERDI RESPIMAT Approved Use The long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Is not indicated to treat acute deterioration of COPD and asthma. Launch Date 2014

C_max

Value	Dose	Co-administered	Analyte	Population
5.92 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26316741	5 μg 1 times / day multiple, respiratory dose: 5 μg route of administration: Respiratory experiment type: MULTIPLE co-administered:		OLODATEROL HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
13.1 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26316741	10 μg 1 times / day multiple, respiratory dose: 10 μg route of administration: Respiratory experiment type: MULTIPLE co-administered:		OLODATEROL HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
104 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26316741	5 μg 1 times / day multiple, respiratory dose: 5 μg route of administration: Respiratory experiment type: MULTIPLE co-administered:		OLODATEROL HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
160 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26316741	10 μg 1 times / day multiple, respiratory dose: 10 μg route of administration: Respiratory experiment type: MULTIPLE co-administered:		OLODATEROL HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203108s008lbl.pdf	5 μg 1 times / day unknown, unknown dose: 5 μg route of administration: UNKNOWN experiment type: UNKNOWN co-administered:		OLODATEROL HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
40% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203108s008lbl.pdf	5 μg 1 times / day unknown, unknown dose: 5 μg route of administration: UNKNOWN experiment type: UNKNOWN co-administered:		OLODATEROL HYDROCHLORIDE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	substrate 1037 inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 CYP1A1 110 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP4A11 21	CYP2C8 693 UGT2B7 389 UGT1A1 418 UGT1A7 236 UGT1A9 380 P-gp 1537	CYP1A2 701 CYP2B6 547 CYP2C8 168 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity
CYP1A1 218	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP4A11 25	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no [IC50 >100 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	no
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=25 Page: 25.0	weak [IC50 100 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=25 Page: 25.0	weak [IC50 365 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=26 Page: 26.0	yes [Ki 1.92 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf#page=8 Page: 8.0	minor	yes (co-administration study) Comment: Ketoconazole: Co-administration of 400 mg ketoconazole once a day for 14 days increased olodaterol Cmax by 66% and AUC0-1 by 68%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf#page=8 Page: 8.0
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf#page=8 Page: 8.0	weak	no (co-administration study) Comment: Co-administration of 400 mg fluconazole once a day for 14 days had no relevant effect on systemic exposure to olodaterol. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf#page=8 Page: 8.0
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf#page=8 Page: 8.0	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000ClinPharmR.pdf#page=3 Page: 3.0	yes
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf#page=8 Page: 8.0	yes
UGT1A7 236	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf#page=8 Page: 8.0	yes
UGT1A9 380	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf#page=8 Page: 8.0	yes
UGT2B7 389	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/203108s000lbl.pdf#page=8 Page: 8.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/203108Orig1s000PharmR.pdf#page=54 Page: 54.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:82700	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:82700
ChemicalBook	CB52484977	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB52484977
MolPort	MolPort-044-183-629	https://www.molport.com/shop/molecule-link/MolPort-044-183-629
ZINC	ZINC000034636383	http://zinc15.docking.org/substances/ZINC000034636383

PubMed

Title	Date	PubMed
Endothelin-1 enhances β₂-adrenoceptor gene transcription in human lung fibroblasts.	2012 Oct 15	22483689
β₂-adrenoceptors and muscarinic receptors mediate opposing effects on endothelin-1 expression in human lung fibroblasts.	2012 Sep 15	22796455

Patents

Sample Use Guides

In Vivo Use Guide

Two inhalations of STRIVERDI RESPIMAT once-daily at the same time of day. Inhalation spray: Each actuation from the mouthpiece contains 2.7 mcg olodaterol hydrochloride, equivalent to 2.5 mcg olodaterol. Two actuations equal one dose.

Route of Administration: Respiratory

In Vitro Use Guide

MRC-5 human lung fibroblasts were cultured in absence or presence of 10 nM olodaterol, followed by ß2-adrenoceptor mRNA determination by quantitative real time PCR

Name

Type

Language

OLODATEROL

Official Name

English

Olodaterol [WHO-DD]

Common Name

English

OLODATEROL HYDROCHLORIDE [JAN]

Common Name

English

BI 1744

Code

English

OLODATEROL [VANDF]

Common Name

English

2H-1,4-BENZOXAZIN-3(4H)-ONE, 6-HYDROXY-8-((1R)-1-HYDROXY-2-((2-(4-METHOXYPHENYL)-1,1-DIMETHYLETHYL)AMINO)ETHYL)-

Systematic Name

English

6-HYDROXY-8-((1R)-1-HYDROXY-2-((1-(4-METHOXYPHENYL)-2-METHYLPROPAN-2-YL)AMINO)ETHYL)-2H-1,4-BENZOXAZIN-3(4H)-ONE

Systematic Name

English

6-HYDROXY-8-((1R)-1-HYDROXY-2-((2-(4-METHOXYPHENYL)-1,1-DIMETHYLETHYL)AMINO)ETHYL)-2H-1,4-BENZOXAZIN-3(4H)-ONE

Systematic Name

English

olodaterol [INN]

Common Name

English

BI-1744

Code

English

OLODATEROL [MI]

Common Name

English

OLODATEROL [USAN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175779