Details of the Drug Combination

General Information of Drug Combination (ID: DC2KP8U)

• Drug Combination Name: Tiotropium + Indacaterol
• Indication: Chronic Obstructive Pulmonary Disease (COPD); Status: Phase 1 [1]
• Component Drugs:
  Tiotropium (DMFDC0Q): Small molecular drug
  Indacaterol (DMQJHR7): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Tiotropium

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Approved	[2]
Pulmonary emphysema	CA21.Z	Approved	[3]
Asthma	CA23	Investigative	[3]

Tiotropium Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Muscarinic acetylcholine receptor (CHRM)	TTOXS3C	NOUNIPROTAC	Antagonist	[6]
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Antagonist	[7]

Tiotropium Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[8]
Organic cation/carnitine transporter 2 (SLC22A5)	DT3HUVD	S22A5_HUMAN	Substrate	[9]

Indication(s) of Indacaterol

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Approved	[4]
Asthma	CA23	Phase 4	[5]

Indacaterol 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	[10]

Indacaterol Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[8]

Indacaterol Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[12]

Indacaterol Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Increases Activity	[13]

References

• [1] ClinicalTrials.gov (NCT00615459) A Crossover Study to Determine the Effect on Lung Function of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control
• [2] 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: 367).
• [3] Tiotropium FDA Label
• [4] 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: 7455).
• [5] ClinicalTrials.gov (NCT00442351) Efficacy and Tolerability of Maintenance Treatment With Asmanex Twisthaler Versus Placebo in Mild/Moderate Persistent Asthmatics (Study P04654)(TERMINATED). U.S. National Institutes of Health.
• [6] 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.
• [7] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [8] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [9] Transport of ipratropium, an anti-chronic obstructive pulmonary disease drug, is mediated by organic cation/carnitine transporters in human bronchial epithelial cells: implications for carrier-mediated pulmonary absorption. Mol Pharm. 2010 Feb 1;7(1):187-95.
• [10] Emerging drugs in chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2009 Mar;14(1):181-94.
• [11] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [12] Use of indacaterol for the treatment of COPD: a pharmacokinetic evaluation. Expert Opin Drug Metab Toxicol. 2014 Jan;10(1):129-37.
• [13] 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.