Details of the Drug Combination

General Information of Drug Combination (ID: DCDARLY)

• Drug Combination Name: Doxofylline + Budesonide
• Indication: Asthma Chronic; Status: Phase 3 [1]
• Component Drugs:
  Doxofylline (DMEDKZH): Small molecular drug
  Budesonide (DMJIBAW): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Doxofylline

Disease Entry	ICD 11	Status	REF
Asthma	CA23	Approved	[2]

Doxofylline Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[6]

Indication(s) of Budesonide

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[3]
Asthma	CA23	Approved	[4]
Crohn disease	DD70	Approved	[3]
Inflammatory bowel disease	DD72	Approved	[3]
Radiation proctitis	N.A.	Approved	[3]
Ulcerative colitis	DD71	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[5]

Budesonide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Antagonist	[8]

Budesonide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[10]

Budesonide Interacts with 28 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Increases Expression	[11]
Metallothionein-2 (MT2A)	OTHOACHD	MT2_HUMAN	Increases Expression	[12]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Decreases Expression	[12]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Expression	[13]
Cytosolic phospholipase A2 (PLA2G4A)	OTE70SOT	PA24A_HUMAN	Decreases Activity	[14]
Organic solute transporter subunit alpha (SLC51A)	OTDJRZ0P	OSTA_HUMAN	Increases Expression	[11]
Organic solute transporter subunit beta (SLC51B)	OT4WYPSR	OSTB_HUMAN	Increases Expression	[11]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[15]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[16]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[17]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Decreases Secretion	[18]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Secretion	[18]
Lactotransferrin (LTF)	OT8JWCZ0	TRFL_HUMAN	Decreases Secretion	[19]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Decreases Expression	[20]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Decreases Secretion	[21]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[22]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[23]
Mineralocorticoid receptor (NR3C2)	OT0F2V2Z	MCR_HUMAN	Increases Activity	[24]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[7]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[22]
Eosinophil cationic protein (RNASE3)	OTVE2XD1	ECP_HUMAN	Decreases Expression	[25]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Increases Expression	[7]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[7]
Interleukin-4 receptor subunit alpha (IL4R)	OTTXOTCW	IL4RA_HUMAN	Decreases Expression	[26]
Interleukin-13 (IL13)	OTI4YS3Y	IL13_HUMAN	Increases Activity	[27]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[28]
C-C motif chemokine 17 (CCL17)	OTIKW21L	CCL17_HUMAN	Decreases Expression	[26]
T-box transcription factor TBX21 (TBX21)	OT3UK5KE	TBX21_HUMAN	Increases Response	[29]

References

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• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Budesonide FDA Label
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• [20] The effects of inhaled glucocorticoids on bone mass and biochemical markers of bone homeostasis: a 1-year study of beclomethasone versus budesonide. Neth J Med. 1997 Jun;50(6):233-7. doi: 10.1016/s0300-2977(96)00081-2.
• [21] 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.
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• [23] 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.
• [24] Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties. Eur J Endocrinol. 2004 Sep;151(3):397-406. doi: 10.1530/eje.0.1510397.
• [25] Effects of different anti-asthmatic agents on induced sputum and eosinophil cationic protein in mild asthmatics. Respirology. 2004 Nov;9(4):514-20. doi: 10.1111/j.1440-1843.2004.00631.x.
• [26] Effect of inhaled corticosteroid on an immunoreactive thymus and activation-regulated chemokine expression in the bronchial biopsies from asthmatics. Allergy. 2005 Mar;60(3):317-22. doi: 10.1111/j.1398-9995.2005.00694.x.
• [27] [Effects of beclomethasone dipropionate and budesonide on interleukin-13 induced cytokine release, proliferation and differentiation of the human lung fibroblasts]. Zhonghua Jie He He Hu Xi Za Zhi. 2007 Aug;30(8):599-604.
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• [29] TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids. Proc Natl Acad Sci U S A. 2004 Dec 28;101(52):18099-104. doi: 10.1073/pnas.0408532102. Epub 2004 Dec 16.