Details of the Drug

General Information of Drug (ID: DMF5EK1)

• Drug Name: Vilanterol
• Synonyms: 503068-34-6; GW642444x; UNII-028LZY775B; GW-642444x; CHEBI:75037; 028LZY775B; Vilanterol (GW642444; GW 642444X); 4-((1R)-2-((6-(2-((2,6-dichlorophenyl)methoxy)ethoxy)hexyl)amino)-1-hydroxyethyl)-2-(hydroxymethyl)phenol; 4-[(1R)-2-[(6-{2-[(2,6-dichlorophenyl)methoxy]ethoxy}hexyl)amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol; Vilanterol [USAN:INN]; vilanterolum; Vilanterol base; Vilanterol (USAN); SCHEMBL142630; GTPL7353; CHEMBL1198857; DTXSID80198318; DAFYYTQWSAWIGS-DEOSSOPVSA-N; MolPort-044-560-195; Relovair

Indication

Disease Entry	ICD 11	Status	REF
Chronic obstructive pulmonary disease	CA22	Approved	[1]
Pulmonary emphysema	CA21.Z	Approved	[2]
Asthma	CA23	Investigative	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 486.4
  Logarithm of the Partition Coefficient (xlogp); 3.8
  Rotatable Bond Count (rotbonds); 16
  Hydrogen Bond Donor Count (hbonddonor); 4
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 25.7 mL/min/kg [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 21.3 hours [3]
  Metabolism: The drug is metabolized via the cytochrome p450 3A4 (CYP3A4) to a range of metabolites with significantly reduced beta1- and beta2-agonist activity []
  Unbound Fraction: The unbound fraction of drug in plasma is 0.06% [3]
  Vd: The volume of distribution (Vd) of drug is 661 L []
• Chemical Identifiers:
  Formula: C24H33Cl2NO5
  IUPAC Name: 4-[(1R)-2-[6-[2-[(2,6-dichlorophenyl)methoxy]ethoxy]hexylamino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol
  Canonical SMILES: C1=CC(=C(C(=C1)Cl)COCCOCCCCCCNC[C@@H](C2=CC(=C(C=C2)O)CO)O)Cl
  InChI: InChI=1S/C24H33Cl2NO5/c25-21-6-5-7-22(26)20(21)17-32-13-12-31-11-4-2-1-3-10-27-15-24(30)18-8-9-23(29)19(14-18)16-28/h5-9,14,24,27-30H,1-4,10-13,15-17H2/t24-/m0/s1
  InChIKey: DAFYYTQWSAWIGS-DEOSSOPVSA-N
• Cross-matching ID:
  PubChem CID: 10184665
  ChEBI ID: CHEBI:75037
  CAS Number: 503068-34-6
  DrugBank ID: DB09082
  TTD ID: D0L0GM
  INTEDE ID: DR1684
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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	Modulator	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Beta-2 adrenergic receptor (ADRB2)	OTSDOX4Q	ADRB2_HUMAN	Gene/Protein Processing	[5]

Molecular Expression Atlas of This Drug

• ICD Disease Classification: 12 Disease of the respiratory system
• Disease Class: ICD-11: CA23 Asthma
• The Studied Tissue: Lung tissue
• The Studied Disease: Chronic obstructive pulmonary disease [ICD-11:CA23]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Adrenergic receptor beta-2 (ADRB2)	DTT	ADRB2	4.88E-01	-0.05	-0.12
Adrenergic receptor beta-2 (ADRB2)	DTT	ADRB2	7.10E-01	0.06	0.09
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	2.13E-01	4.03E-02	2.50E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	8.21E-02	8.17E-02	4.35E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Vilanterol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Moderate	Additive hypertensive effects by the combination of Vilanterol and Methylene blue.	Acquired methaemoglobinaemia [3A93]	[6]
Ivosidenib	DM8S6T7	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Ivosidenib.	Acute myeloid leukaemia [2A60]	[7]
Arn-509	DMT81LZ	Moderate	Increased risk of ventricular arrhythmias by the combination of Vilanterol and Arn-509.	Acute myeloid leukaemia [2A60]	[7]
Gilteritinib	DMTI0ZO	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Gilteritinib.	Acute myeloid leukaemia [2A60]	[7]
Oliceridine	DM6MDCF	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Oliceridine.	Acute pain [MG31]	[7]
Ivabradine	DM0L594	Moderate	Increased risk of ventricular arrhythmias by the combination of Vilanterol and Ivabradine.	Angina pectoris [BA40]	[7]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Vilanterol caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[8]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Vilanterol caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[9]
PF-04449913	DMSB068	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[7]
Osilodrostat	DMIJC9X	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Osilodrostat.	Cushing syndrome [5A70]	[7]
Deutetrabenazine	DMUPFLI	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Deutetrabenazine.	Dystonic disorder [8A02]	[7]
Ingrezza	DMVPLNC	Moderate	Increased risk of ventricular arrhythmias by the combination of Vilanterol and Ingrezza.	Dystonic disorder [8A02]	[7]
Fostemsavir	DM50ILT	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[7]
Osimertinib	DMRJLAT	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Osimertinib.	Lung cancer [2C25]	[7]
Selpercatinib	DMZR15V	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Selpercatinib.	Lung cancer [2C25]	[7]
LGX818	DMNQXV8	Moderate	Increased risk of ventricular arrhythmias by the combination of Vilanterol and LGX818.	Melanoma [2C30]	[7]
Siponimod	DM2R86O	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Siponimod.	Multiple sclerosis [8A40]	[7]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Vilanterol and Ozanimod.	Multiple sclerosis [8A40]	[10]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Rucaparib.	Ovarian cancer [2C73]	[7]
Triclabendazole	DMPWGBR	Moderate	Increased risk of ventricular arrhythmias by the combination of Vilanterol and Triclabendazole.	Parasitic worm infestation [1F90]	[7]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Vilanterol caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[11]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Vilanterol and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[12]
Lefamulin	DME6G97	Moderate	Increased risk of ventricular arrhythmias by the combination of Vilanterol and Lefamulin.	Pneumonia [CA40]	[7]
Relugolix	DMK7IWL	Moderate	Increased risk of prolong QT interval by the combination of Vilanterol and Relugolix.	Prostate cancer [2C82]	[7]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of Vilanterol and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[13]
Pitolisant	DM8RFNJ	Moderate	Increased risk of ventricular arrhythmias by the combination of Vilanterol and Pitolisant.	Somnolence [MG42]	[7]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Vilanterol caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[14]
Fluticasone	DMGCSVF	Minor	Increased risk of hypokalemia by the combination of Vilanterol and Fluticasone.	Vasomotor/allergic rhinitis [CA08]	[15]

References

• [1] 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: 7353).
• [2] Vilanterol FDA Label
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of inhaled fluticasone furoate and vilanterol trifenatate in healthy subjects. Br J Clin Pharmacol. 2013 Jun;75(6):1478-87.
• [5] 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.
• [6] Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Prichard BN "Interactions between sympathomimetic amines and antidepressant agents in man." Br Med J 1 (1973): 311-5. [PMID: 4685619]
• [7] Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
• [8] Product Information. Sonata (zaleplon) Wyeth-Ayerst Laboratories, Philadelphia, PA.
• [9] Product Information. Breo Ellipta (fluticasone-vilanterol). GlaxoSmithKline, Research Triangle Park, NC.
• [10] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
• [11] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [12] Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
• [13] Canadian Pharmacists Association.
• [14] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
• [15] Cerner Multum, Inc. "Australian Product Information.".