Details of the Drug Combination

General Information of Drug Combination (ID: DCARMFG)

• Drug Combination Name: Levalbuterol + Arformoterol
• Indication: Asthma; Status: Phase 1 [1]
• Component Drugs:
  Levalbuterol (DM5YBO1): Small molecular drug
  Arformoterol (DMYM974): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Levalbuterol

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

Levalbuterol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-2 (ADRB2)	TT2CJVK	ADRB2_HUMAN	Antagonist	[6]

Indication(s) of Arformoterol

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Approved	[3]
Pulmonary emphysema	CA21.Z	Approved	[4]
Asthma	CA23	Phase 4	[5]

Arformoterol Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adrenergic receptor beta-2 (ADRB2)	TT2CJVK	ADRB2_HUMAN	Agonist	[7]

Arformoterol Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2A6 (CYP2A6)	DEJVYAZ	CP2A6_HUMAN	Metabolism	[8]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[8]

Arformoterol Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Activity	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[10]
Eosinophil cationic protein (RNASE3)	OTVE2XD1	ECP_HUMAN	Decreases Expression	[11]
Actin, aortic smooth muscle (ACTA2)	OTEDLG8E	ACTA_HUMAN	Decreases Expression	[12]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[13]
Solute carrier family 22 member 3 (SLC22A3)	OTQYGVXX	S22A3_HUMAN	Increases Uptake	[14]

References

• [1] ClinicalTrials.gov (NCT00583947) A Safety and Tolerability Study of Arformoterol Tartrate Inhalation Solution in Pediatric Subjects
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] 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: 7479).
• [4] Arformoterol FDA Label
• [5] ClinicalTrials.gov (NCT02491970) Study to Evaluate Small Airway Parameters of Fluticasone/Formoterol (Flutiform) Compared to Fluticasone/Salmeterol in Asthma Patients.
• [6] Beta-blockers in the treatment of hypertension: are there clinically relevant differences Postgrad Med. 2009 May;121(3):90-8.
• [7] Arformoterol tartrate in the treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease. Drugs Today (Barc). 2009 Jan;45(1):3-9.
• [8] A comparison of the expression and metabolizing activities of phase I and II enzymes in freshly isolated human lung parenchymal cells and cryopreserved human hepatocytes. Drug Metab Dispos. 2007 Oct;35(10):1797-805.
• [9] Development of 3D-QSAR models for predicting the activities of chemicals to stimulate muscle growth via (2)-adrenoceptor. Toxicol In Vitro. 2021 Dec;77:105251. doi: 10.1016/j.tiv.2021.105251. Epub 2021 Sep 30.
• [10] Long-acting beta2-adrenergic formoterol and salmeterol induce the apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 2004 Jan;124(2):141-50. doi: 10.1046/j.1365-2141.2003.04746.x.
• [11] Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses. Am Rev Respir Dis. 1992 Nov;146(5 Pt 1):1156-60. doi: 10.1164/ajrccm/146.5_Pt_1.1156.
• [12] The 2-subtype of adrenoceptors mediates inhibition of pro-fibrotic events in human lung fibroblasts. Naunyn Schmiedebergs Arch Pharmacol. 2011 Aug;384(2):133-45. doi: 10.1007/s00210-011-0655-5. Epub 2011 May 21.
• [13] Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
• [14] The effect of corticosteroids on the disposal of long-acting beta2-agonists by airway smooth muscle cells. J Allergy Clin Immunol. 2007 Nov;120(5):1103-9. doi: 10.1016/j.jaci.2007.08.034. Epub 2007 Oct 17.