Details of the Drug Combination

General Information of Drug Combination (ID: DCMZHJ2)

• Drug Combination Name: Budesonide + Montelukast
• Indication: Asthma; Status: Phase 1 [1]
• Component Drugs:
  Budesonide (DMJIBAW): Small molecular drug
  Montelukast (DMD157S): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Budesonide

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[2]
Asthma	CA23	Approved	[3]
Crohn disease	DD70	Approved	[2]
Inflammatory bowel disease	DD72	Approved	[2]
Radiation proctitis	N.A.	Approved	[2]
Ulcerative colitis	DD71	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]

Budesonide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Antagonist	[9]

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	[10]
Sulfotransferase 1A1 (SULT1A1)	DEYWLRK	ST1A1_HUMAN	Metabolism	[11]

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	[12]
Metallothionein-2 (MT2A)	OTHOACHD	MT2_HUMAN	Increases Expression	[13]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Decreases Expression	[13]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Expression	[14]
Cytosolic phospholipase A2 (PLA2G4A)	OTE70SOT	PA24A_HUMAN	Decreases Activity	[15]
Organic solute transporter subunit alpha (SLC51A)	OTDJRZ0P	OSTA_HUMAN	Increases Expression	[12]
Organic solute transporter subunit beta (SLC51B)	OT4WYPSR	OSTB_HUMAN	Increases Expression	[12]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[16]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Activity	[17]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[18]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Decreases Secretion	[19]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Secretion	[19]
Lactotransferrin (LTF)	OT8JWCZ0	TRFL_HUMAN	Decreases Secretion	[20]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Decreases Expression	[21]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Decreases Secretion	[22]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Expression	[23]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[24]
Mineralocorticoid receptor (NR3C2)	OT0F2V2Z	MCR_HUMAN	Increases Activity	[25]
C-C motif chemokine 3 (CCL3)	OTW2H3ND	CCL3_HUMAN	Increases Expression	[8]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[23]
Eosinophil cationic protein (RNASE3)	OTVE2XD1	ECP_HUMAN	Decreases Expression	[26]
C-C motif chemokine 4 (CCL4)	OT6B8P25	CCL4_HUMAN	Increases Expression	[8]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Decreases Expression	[8]
Interleukin-4 receptor subunit alpha (IL4R)	OTTXOTCW	IL4RA_HUMAN	Decreases Expression	[27]
Interleukin-13 (IL13)	OTI4YS3Y	IL13_HUMAN	Increases Activity	[28]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[29]
C-C motif chemokine 17 (CCL17)	OTIKW21L	CCL17_HUMAN	Decreases Expression	[27]
T-box transcription factor TBX21 (TBX21)	OT3UK5KE	TBX21_HUMAN	Increases Response	[30]

Indication(s) of Montelukast

Disease Entry	ICD 11	Status	REF
Allergic asthma	CA23.0	Approved	[5]
Allergic rhinitis	CA08.0	Approved	[5]
Asthma	CA23	Approved	[6]
Intrinsic asthma	N.A.	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2/3	[7]

Montelukast Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HUMAN cysteinyl leukotriene receptor (CysLTR)	TTSB6CA	CLTR1_HUMAN; CLTR2_HUMAN	Antagonist	[31]
Leukotriene CysLT1 receptor (CYSLTR1)	TTGKOY9	CLTR1_HUMAN	Antagonist	[32]

Montelukast Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic anion transporting polypeptide 1A2 (SLCO1A2)	DTE2B1D	SO1A2_HUMAN	Substrate	[33]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[34]

Montelukast Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[35]
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[35]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[36]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[37]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Obstructive Sleep Apnea Syndrome	DC3E7D3	N. A.	Phase 1	[38]

References

• [1] ClinicalTrials.gov (NCT00462592) Comparison of Combination Therapy: Montelukast and Inhaled Steroid on Exercise Induced Bronchoconstriction
• [2] Budesonide FDA Label
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• [4] Inhaled Corticosteroid Treatment of COVID19 Patients With Pneumonia
• [5] Montelukast FDA Label
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3340).
• [7] The COvid-19 Symptom MOntelukast Trial (COSMO)
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• [22] 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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• [24] 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.
• [25] 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.
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• [28] [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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• [34] Effects of polymorphisms of the SLCO2B1 transporter gene on the pharmacokinetics of montelukast in humans. J Clin Pharmacol. 2013 Nov;53(11):1186-93.
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• [38] ClinicalTrials.gov (NCT00912171) Efficacy of Oral Leukotriene in Long Term Therapy of Mild and Moderate Obstructive Sleep Apnea Syndrome in Children