Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMGQSVX)

• Drug Name: AZD-2115 Drug Info
• Synonyms: Dual action MABA (COPD), AstraZeneca; Dual action muscarinic acetylcholine receptor antagonist/beta 2 adrenoceptor agonist (COPD), AstraZeneca

Indication

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Phase 2	[1]

• Cross-matching ID: TTD Drug ID: DMGQSVX

Molecule-Related Drug Atlas

Drug(s) Targeting Muscarinic acetylcholine receptor (CHRM)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetylcholine	DMDF79Z	Cataract	9B10	Approved	[3]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[4]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[5]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[6]
Clidinium	DMUMQZ0	Abdominal stomach pain	DD91.4	Approved	[7]
Oxybutynin hydrochloride	DMF2KLU	Urinary incontinence	MF50.2	Approved	[8]
Incruse Ellipta	DM32GSJ	Chronic obstructive pulmonary disease	CA22	Approved	[9]
Revefenacin	DMMP5SI	Chronic obstructive pulmonary disease	CA22	Approved	[10]
Scopolamine	DMOM8AL	Addictive disorder	6C50-6C5Z	Approved	[11]
Isopropamide iodide	DMQYV60	Allergic rhinitis	CA08.0	Approved	[12]

Drug(s) Targeting Adrenergic receptor beta-2 (ADRB2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Indacaterol	DMQJHR7	Chronic obstructive pulmonary disease	CA22	Approved	[13]
Formoterol	DMSOURV	Allergic asthma	CA23.0	Approved	[14]
Salbutamol	DMN9CWF	Acute asthma	CA23	Approved	[15]
Arformoterol	DMYM974	Chronic obstructive pulmonary disease	CA22	Approved	[16]
Isoproterenol	DMK7MEY	Atrioventricular block		Approved	[17]
Salmeterol	DMIEU69	Allergic asthma	CA23.0	Approved	[18]
Clenbuterol	DMCKYZ5	Chronic breathing disorder	7A4Z	Approved	[19]
Ritodrine	DM4V6RL	Premature labour	JB00	Approved	[20]
Olodaterol	DM62B78	Chronic obstructive pulmonary disease	CA22	Approved	[21]
Fenoterol	DMIP3ZV	Asthma	CA23	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor beta-2 (ADRB2)	TT2CJVK	ADRB2_HUMAN	Agonist	[2]
Muscarinic acetylcholine receptor (CHRM)	TTOXS3C	NOUNIPROTAC	Agonist	[2]

References

• [1] ClinicalTrials.gov (NCT02109406) Efficacy and Safety Study of Two Dose Levels of AZD2115 in Subjects With Moderate to Severe COPD. U.S. National Institutes of Health.
• [2] Evaluation of WO-2012085582 and WO-2012085583 two identified MABAs: backups to AZD-2115. Expert Opin Ther Pat. 2012 Nov;22(11):1377-83.
• [3] Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.
• [4] Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases. J Pharmacol Exp Ther. 2013 May;345(2):260-70.
• [5] Characterisation of [3H]-darifenacin as a novel radioligand for the study of muscarinic M3 receptors. J Recept Signal Transduct Res. 1997 Jan-May;17(1-3):177-84.
• [6] Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.
• [7] Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. J Pharmacol Exp Ther. 1998 Feb;284(2):500-7.
• [8] Effects of propiverine hydrochloride (propiverine) on the muscarinic receptor binding affinity in guinea pig tissues and on salivation in conscious dogs. Nihon Yakurigaku Zasshi. 1999 Mar;113(3):157-66.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline.
• [10] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [11] The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors. Neuroscience. 2009 May 5;160(2):255-63.
• [12] Competitive and non-competitive antagonism exhibited by 'selective' antagonists at atrial and ileal muscarinic receptor subtypes. Br J Pharmacol. 1987 Apr;90(4):701-7.
• [13] Emerging drugs in chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2009 Mar;14(1):181-94.
• [14] Long-acting beta2-agonists for chronic obstructive pulmonary disease patients with poorly reversible airflow limitation. Cochrane Database Syst Rev. 2002;(3):CD001104.
• [15] Potential of beta2-adrenoceptor agonists as add-on therapy for multiple sclerosis: focus on salbutamol (albuterol). CNS Drugs. 2002;16(1):1-8.
• [16] Arformoterol tartrate in the treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease. Drugs Today (Barc). 2009 Jan;45(1):3-9.
• [17] Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists. Eur J Clin Pharmacol. 1998 Feb;53(6):389-404.
• [18] Pharmacogenetic tests in asthma therapy. Clin Lab Med. 2008 Dec;28(4):645-65.
• [19] Postischemic brain injury is attenuated in mice lacking the beta2-adrenergic receptor. Anesth Analg. 2009 Jan;108(1):280-7.
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [21] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [22] Functional alpha1- and beta2-adrenergic receptors in human osteoblasts. J Cell Physiol. 2009 Jul;220(1):267-75.