Details of the Drug Combination

General Information of Drug Combination (ID: DCW4LI3)

Drug Combination Name

Fluticasone propionate GW685698X

Indication

Disease Entry	Status	REF
Asthma	Phase 1	[1]

Component Drugs

Fluticasone propionate DMRWLB2

GW685698X DML72VJ

N.A.

Small molecular drug

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Fluticasone propionate

Disease Entry	ICD 11	Status	REF
Allergic asthma	CA23.0	Approved	[2]
Allergic rhinitis	CA08.0	Approved	[2]
Bronchiolitis	N.A.	Approved	[2]
Exanthem	N.A.	Approved	[2]
Granuloma annulare	N.A.	Approved	[2]
Intrinsic asthma	N.A.	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[2]
Pulmonary emphysema	CA21.Z	Approved	[2]

Fluticasone propionate Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
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Fluticasone propionate Interacts with 15 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Secretion	[7]
Glutathione hydrolase 5 proenzyme (GGT5)	OTDJYEO7	GGT5_HUMAN	Increases Expression	[8]
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Activity	[9]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Expression	[10]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[11]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Increases Expression	[12]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[13]
Annexin A1 (ANXA1)	OT5OFDJC	ANXA1_HUMAN	Affects Localization	[14]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Decreases Secretion	[15]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Affects Localization	[13]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[16]
Protein kinase C alpha type (PRKCA)	OT5UWNRD	KPCA_HUMAN	Decreases Expression	[16]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Decreases Activity	[17]
Dual specificity protein phosphatase 1 (DUSP1)	OTN6BR75	DUS1_HUMAN	Increases Expression	[13]
Cytosolic phospholipase A2 (PLA2G4A)	OTE70SOT	PA24A_HUMAN	Affects Localization	[14]
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⏷ Show the Full List of 15 DOT(s)

Indication(s) of GW685698X

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[3]
Asthma	CA23	Approved	[4]

GW685698X Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Agonist	[18]
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References

1	Fluticasone furoate/fluticasone propionate - different drugs with different properties. Clin Respir J. 2011 July; 5(3): 183-184.
2	Fluticasone propionate FDA Label
3	A standard database for drug repositioning. Sci Data. 2017 Mar 14;4:170029.
4	ClinicalTrials.gov (NCT00539006) Comparator Study Evaluating Patient Preference Of FFNS vs. FPNS. U.S. National Institutes of Health.
5	Inhibition of VCAM-1 expression in human bronchial epithelial cells by glucocorticoids. Am J Respir Cell Mol Biol. 1999 Apr;20(4):643-50. doi: 10.1165/ajrcmb.20.4.3265.
6	Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated efflux. Toxicol Appl Pharmacol. 2012 May 1;260(3):294-302.
7	Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated efflux. Toxicol Appl Pharmacol. 2012 May 1;260(3):294-302. doi: 10.1016/j.taap.2012.03.008. Epub 2012 Mar 23.
8	A novel pharmacologic action of glucocorticosteroids on leukotriene C4 catabolism. J Allergy Clin Immunol. 2001 Jul;108(1):122-4.
9	The inhaled glucocorticoid fluticasone propionate efficiently inactivates cytochrome P450 3A5, a predominant lung P450 enzyme. Chem Res Toxicol. 2010 Aug 16;23(8):1356-64.
10	Regulation of CYP3A genes by glucocorticoids in human lung cells. F1000Res. 2013 Aug 13;2:173.
11	Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening. Drug Metab Dispos. 2011 Feb;39(2):337-44. doi: 10.1124/dmd.110.035808. Epub 2010 Nov 10.
12	Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate. Respirology. 2001 Sep;6(3):237-46. doi: 10.1046/j.1440-1843.2001.00329.x.
13	Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy. Am J Respir Crit Care Med. 2005 Sep 15;172(6):704-12. doi: 10.1164/rccm.200408-1041OC. Epub 2005 Apr 28.
14	Glucocorticoid-induced surface expression of annexin 1 blocks beta2-integrin adhesion of human eosinophils to intercellular adhesion molecule 1 surrogate protein. J Allergy Clin Immunol. 2005 Mar;115(3):493-500. doi: 10.1016/j.jaci.2004.11.010.
15	Inhibition of GM-CSF secretion by topical corticosteroids and nedocromil sodium. A comparison study using nasal polyp epithelial cells. Respir Med. 2000 May;94(5):428-31. doi: 10.1053/rmed.1999.0756.
16	[The effect of inhaled glucocorticosteroid on protein kinase C alpha expression and interleukin-5 production in induced sputum inflammatory cells of asthma patients]. Zhonghua Nei Ke Za Zhi. 2004 Nov;43(11):849-52.
17	Association of human serum paraoxonase-1 with some respiratory drugs. J Biochem Mol Toxicol. 2019 Dec;33(12):e22407. doi: 10.1002/jbt.22407. Epub 2019 Oct 3.
18	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).