FLUTICASONE FUROATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H29F3O6S
Molecular Weight	538.576
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@@H](C)[C@](OC(=O)C3=CC=CO3)(C(=O)SCF)[C@@]1(C)C[C@H](O)[C@@]4(F)[C@@]2([H])C[C@H](F)C5=CC(=O)C=C[C@]45C

InChI

InChIKey=XTULMSXFIHGYFS-VLSRWLAYSA-N

InChI=1S/C27H29F3O6S/c1-14-9-16-17-11-19(29)18-10-15(31)6-7-24(18,2)26(17,30)21(32)12-25(16,3)27(14,23(34)37-13-28)36-22(33)20-5-4-8-35-20/h4-8,10,14,16-17,19,21,32H,9,11-13H2,1-3H3/t14-,16+,17+,19+,21+,24+,25+,26+,27+/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/pro/veramyst.html | http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205625s000lbl.pdf | http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204275s000lbl.pdf | http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022051s011lbl.pdf

Fluticasone furoate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. Fluticasone furoate is a anti-allergic agents that is FDA approved for the treatment of symptoms of seasonal and perennial allergic rhinitis, asthma and for reducing exacerbations in patients with chronic obstructive pulmonary disease. Fluticasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor. The clinical relevance of these findings is unknown. The most common adverse reactions (>1% incidence) included headache, epistaxis, pharyngolaryngeal pain, nasal ulceration, back pain, pyrexia, and cough. Coadministration of ritonavir is not recommended. Use caution with coadministration of other potent CYP3A4 inhibitors, such as ketoconazole.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Glucocorticoid receptor 172 Target ID: CHEMBL2034 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022051s011lbl.pdf \| http://www.genome.jp/dbget-bin/www_bget?D06315 \| https://www.ncbi.nlm.nih.gov/pubmed/18522385	Agonist 2678	0.3 nM [Kd]
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205625s000lbl.pdf	Substrate 661
Cytochrome P450 2C8 18 Target ID: CHEMBL3721 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000770/WC500028817.pdf	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Perennial or seasonal allergic rhinitis 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022051s011lbl.pdf	Palliative	Approved 8429	Veramyst Approved Use Veramyst is indicated for the treatment of the symptoms of seasonal and perennial allergic rhinitis in patients aged 2 years and older. Launch Date 2007
Asthma 241 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205625s000lbl.pdf	Preventing	Approved 8429	ARNUITY ELLIPTA Approved Use RNUITY™ ELLIPTA® is indicated for the once-daily maintenance treatment of asthma as prophylactic therapy in patients aged 12 years and older. Launch Date 2014
Chronic obstructive pulmonary disease 174 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204275s000lbl.pdf	Primary	Approved 8429	BREO ELLIPTA Approved Use BREO® ELLIPTA® 100/25 is a combination inhaled corticosteroid/long-acting beta2-adrenergic agonist (ICS/LABA) indicated 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. Launch Date 2013

C_max

Value	Dose	Co-administered	Analyte	Population
4224 pg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27163502	250 μg single, intravenous dose: 250 μg route of administration: Intravenous experiment type: SINGLE co-administered:		FLUTICASONE FUROATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3505 pg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27163502	250 μg single, intravenous dose: 250 μg route of administration: Intravenous experiment type: SINGLE co-administered:		FLUTICASONE FUROATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27163502	250 μg single, intravenous dose: 250 μg route of administration: Intravenous experiment type: SINGLE co-administered:		FLUTICASONE FUROATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.6% EXPERIMENT https://link.springer.com/article/10.2165/00003495-200767130-00010			FLUTICASONE FUROATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
250 ug single, intravenous Highest studied dose Dose: 250 ug Route: intravenous Route: single Dose: 250 ug Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	healthy, 20-59 years n = 79 Health Status: healthy Age Group: 20-59 years Sex: M+F Population Size: 79 Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	Other AEs: Headache, Catheter site pain... Other AEs: Headache (48 patients) Catheter site pain (26 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/24152086
800 ug 1 times / day multiple, respiratory Highest studied dose Dose: 800 ug, 1 times / day Route: respiratory Route: multiple Dose: 800 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	healthy, 20-59 years n = 79 Health Status: healthy Age Group: 20-59 years Sex: M+F Population Size: 79 Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	Other AEs: Headache, Excoriation... Other AEs: Headache (68 patients) Excoriation (11 patient) Lethargy (10 patients) Diarrhoea (10 patients) Oropharyngeal pain (42 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/24152086
880 ug single, intranasal Dose: 880 ug Route: intranasal Route: single Dose: 880 ug Sources: https://pubmed.ncbi.nlm.nih.gov/32485781	healthy, 40.5 ± 12.4 years (range: 22–59 years) n = 17 Health Status: healthy Age Group: 40.5 ± 12.4 years (range: 22–59 years) Sex: M+F Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/32485781	Other AEs: Headache... Other AEs: Headache (mild, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/32485781

AEs

AE	Significance	Dose	Population
Catheter site pain	26 patients	250 ug single, intravenous Highest studied dose Dose: 250 ug Route: intravenous Route: single Dose: 250 ug Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	healthy, 20-59 years n = 79 Health Status: healthy Age Group: 20-59 years Sex: M+F Population Size: 79 Sources: https://pubmed.ncbi.nlm.nih.gov/24152086
Headache	48 patients	250 ug single, intravenous Highest studied dose Dose: 250 ug Route: intravenous Route: single Dose: 250 ug Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	healthy, 20-59 years n = 79 Health Status: healthy Age Group: 20-59 years Sex: M+F Population Size: 79 Sources: https://pubmed.ncbi.nlm.nih.gov/24152086
Diarrhoea	10 patients	800 ug 1 times / day multiple, respiratory Highest studied dose Dose: 800 ug, 1 times / day Route: respiratory Route: multiple Dose: 800 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	healthy, 20-59 years n = 79 Health Status: healthy Age Group: 20-59 years Sex: M+F Population Size: 79 Sources: https://pubmed.ncbi.nlm.nih.gov/24152086
Lethargy	10 patients	800 ug 1 times / day multiple, respiratory Highest studied dose Dose: 800 ug, 1 times / day Route: respiratory Route: multiple Dose: 800 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	healthy, 20-59 years n = 79 Health Status: healthy Age Group: 20-59 years Sex: M+F Population Size: 79 Sources: https://pubmed.ncbi.nlm.nih.gov/24152086
Excoriation	11 patient	800 ug 1 times / day multiple, respiratory Highest studied dose Dose: 800 ug, 1 times / day Route: respiratory Route: multiple Dose: 800 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	healthy, 20-59 years n = 79 Health Status: healthy Age Group: 20-59 years Sex: M+F Population Size: 79 Sources: https://pubmed.ncbi.nlm.nih.gov/24152086
Oropharyngeal pain	42 patients	800 ug 1 times / day multiple, respiratory Highest studied dose Dose: 800 ug, 1 times / day Route: respiratory Route: multiple Dose: 800 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	healthy, 20-59 years n = 79 Health Status: healthy Age Group: 20-59 years Sex: M+F Population Size: 79 Sources: https://pubmed.ncbi.nlm.nih.gov/24152086
Headache	68 patients	800 ug 1 times / day multiple, respiratory Highest studied dose Dose: 800 ug, 1 times / day Route: respiratory Route: multiple Dose: 800 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24152086	healthy, 20-59 years n = 79 Health Status: healthy Age Group: 20-59 years Sex: M+F Population Size: 79 Sources: https://pubmed.ncbi.nlm.nih.gov/24152086
Headache	mild, 2 patients	880 ug single, intranasal Dose: 880 ug Route: intranasal Route: single Dose: 880 ug Sources: https://pubmed.ncbi.nlm.nih.gov/32485781	healthy, 40.5 ± 12.4 years (range: 22–59 years) n = 17 Health Status: healthy Age Group: 40.5 ± 12.4 years (range: 22–59 years) Sex: M+F Population Size: 17 Sources: https://pubmed.ncbi.nlm.nih.gov/32485781

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2B6 810 CYP2C19 1478 CYP1A2 1524 CYP2A6 707 CYP2E1 882 OATP1B1 788 P-gp 1461	P-gp 1537	CYP 76

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33,36	no [IC50 >100 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33,36	no [IC50 >100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33,36	no [IC50 >100 uM]
CYP 147	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205625Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=34 Page: 34.0	no	GW694301X 1
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=34 Page: 34.0	no	GW694301X 1
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=34 Page: 34.0	no	GW694301X 1
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=34 Page: 34.0	no	GW694301X 1
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=34 Page: 34.0	no	GW694301X 1
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=34 Page: 34.0	no	GW694301X 1
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=34 Page: 34.0	no	GW694301X 1
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=34 Page: 34.0	no	GW694301X 1
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=34 Page: 34.0	no	GW694301X 1
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33.0	no	GW694301X 1
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205625Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	yes [IC50 0.2 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33,36	yes [IC50 0.58 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33,36	yes [IC50 0.74 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33,36	yes [IC50 2.4 uM]
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205625Orig1s000ClinPharmR.pdf#page=35 Page: 35.0	yes [IC50 2.6 uM]	GW694301X 1
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33,36	yes [IC50 3.2 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33,36	yes [IC50 4 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33,36	yes [IC50 5.5 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022051s000_PharmR.pdf#page=33 Page: 33.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205625Orig1s000ClinPharmR.pdf#page=34 Page: 11;34	yes		weak (co-administration study) Comment: administered with ketoconazole; modest increase in mean FF AUC(0-24) and Cmax (by 36% and 33%, respectively) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205625Orig1s000ClinPharmR.pdf#page=34 Page: 11;34

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204275Orig1s000PharmR.pdf#page=50 Page: 50.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:74899	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:74899
ChemicalBook	CB51509114	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB51509114
MolPort	MolPort-046-689-831	https://www.molport.com/shop/molecule-link/MolPort-046-689-831
ZINC	ZINC000003992105	http://zinc15.docking.org/substances/ZINC000003992105
eMolecules	36758202	https://www.emolecules.com/cgi-bin/more?vid=36758202

PubMed

Title	Date	PubMed
Inhaled corticosteroid and long-acting β2-agonist pharmacological profiles: effective asthma therapy in practice.	2012 Dec	23273165
Inhaled fluticasone furoate/vilanterol does not affect hypothalamic-pituitary-adrenal axis function in adolescent and adult asthma: randomised, double-blind, placebo-controlled study.	2013 Oct	23578031

Patents

Sample Use Guides

In Vivo Use Guide

Adults and adolescents ≥12 years: 110 ug (2 sprays per nostril) once daily

Route of Administration: Nasal

In Vitro Use Guide

The potency of fluticasone furoate in PBMCs from mild asthma (IC50: 1.9±0.64 nM, n= 4) was 2.1 fold higher than fluticasone propionate (4.0±1.6 nM, n= 4).

Name

Type

Language

FLUTICASONE FUROATE

Official Name

English

TRELEGY ELLIPTA COMPONENT FLUTICASONE FUROATE

Brand Name

English

FLUTICASONE FUROATE [VANDF]

Common Name

English

Fluticasone Furoate [WHO-DD]

Common Name

English

ALLERMIST

Brand Name

English

GSK 685 698

Code

English

FLUTICASONE FUROATE [JAN]

Common Name

English

FLUTICASONE FUROATE [MART.]

Common Name

English

GSK685968

Code

English

(6.ALPHA.,11.BETA.,16.ALPHA.,17.ALPHA.)-6,9-DIFLUORO-17-(((FLUORO-METHYL)THIO)CARBONYL)-11-HYDROXY-16-METHYL-3-OXOANDROSTA-1,4-DIEN-17-YL 2-FURANCARBOXYLATE

Systematic Name

English

FLUTICASONE FUROATE COMPONENT OF TRELEGY ELLIPTA

Brand Name

English

ANDROSTA-1,4-DIENE-17-CARBOTHIOIC ACID, 6,9-DIFLUORO-17-((2-FURANYLCARBONYL)OXY)-11-HYDROXY-16-METHYL-3-OXO-, S-(FLUOROMETHYL) ESTER, (6.ALPHA.,11.BETA.,16.ALPHA.,17.ALPHA.)-

Common Name

English

GW685698X

Code

English

FURAMIST

Brand Name

English

GSK-685968

Code

English

FLUTICASONE FUROATE COMPONENT OF ARNUITY ELLIPTA

Brand Name

English

FLUTICASONE FUROATE [EMA EPAR]

Common Name

English

(6.ALPHA.,11.BETA.,16.ALPHA.,17.ALPHA.)-6,9-DIFLUORO-17-(((FLUOROMETHYL)THIO)CARBONYL)-11-HYDROXY-16-METHYL-3-OXOANDROSTA-1,4-DIEN-17-YL-2-FURANCARBOXYLATE

Common Name

English

BREO ELLIPTA COMPONENT FLUTICASONE FUROATE

Brand Name

English

(6.ALPHA.,11.BETA.,16.ALPHA.,17.ALPHA.)-6,9-DIFLUORO-17-(((FLUOROMETHYL)THIO)CARBONYL)-11-HYDROXY-16-METHYL-3-OXOANDROSTA-1,4-DIEN-17-YL 2-FUROATE

Common Name

English

fluticasone furoate [INN]

Common Name

English

ENNHALE

Brand Name

English

FLUTICASONE FUROATE COMPONENT OF BREO ELLIPTA

Brand Name

English

FLUTICASONE FUROATE [MI]

Common Name

English

FLUTICASONE FUROATE [ORANGE BOOK]

Common Name

English

FLUTICASONE FUROATE [USAN]

Common Name

English

ARNUITY ELLIPTA COMPONENT FLUTICASONE FUROATE

Brand Name

English

AVAMYS

Brand Name

English

VERAMYST

Brand Name

English

6α,9-Difluoro-17-[[(fluoromethyl)sulfanyl]carbonyl]-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-dien-17α-yl furan-2-carboxylate

Common Name

English

GW-685698X

Code

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

RELVAR ELLIPTA (AUTHORIZED: PULMONARY DISEASE, CHRONIC OBSTRUCTIVE)