Details of the Drug

General Information of Drug (ID: DM32GSJ)

• Drug Name: Incruse ellipta
• Synonyms: Umeclidinium bromide; 869113-09-7; Umeclidinium (bromide); GSK573719A; Incruse Ellipta; UNII-7AN603V4JV; 7AN603V4JV; GSK-573719; 1-[2-(Benzyloxy)ethyl]-4-(hydroxydiphenylmethyl)-1-quinuclidinium Bromide; 1-(2-(benzyloxy)ethyl)-4-(hydroxydiphenylmethyl)quinuclidin-1-ium bromide; CHEMBL523299; Umeclidinium brom; Umeclidinium bromide [USAN:INN]; umeclidinii bromidum; 1-Azoniabicyclo[2.2.2]octane, 4-(hydroxydiphenylmethyl)-1-[2-(phenylmethoxy)ethyl]-, bromide (1:1); 1-Azoniabicyclo(2.2.2)octane, 4-(hydroxydiphenylmethyl)-1-(2

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight; 508.5
  Topological Polar Surface Area; Not Available
  Rotatable Bond Count; 8
  Hydrogen Bond Donor Count; 1
  Hydrogen Bond Acceptor Count; 3
• ADMET Property:
  Clearance: The drug present in the plasma can be removed from the body at the rate of 35.95 mL/min/kg [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 19 hours [2]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.11% [2]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.23 L/kg [2]
• Chemical Identifiers:
  Formula: C29H34BrNO2
  IUPAC Name: diphenyl-[1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-4-yl]methanol;bromide
  Canonical SMILES: C1C[N+]2(CCC1(CC2)C(C3=CC=CC=C3)(C4=CC=CC=C4)O)CCOCC5=CC=CC=C5.[Br-]
  InChI: InChI=1S/C29H34NO2.BrH/c31-29(26-12-6-2-7-13-26,27-14-8-3-9-15-27)28-16-19-30(20-17-28,21-18-28)22-23-32-24-25-10-4-1-5-11-25;/h1-15,31H,16-24H2;1H/q+1;/p-1
  InChIKey: PEJHHXHHNGORMP-UHFFFAOYSA-M
• Cross-matching ID:
  PubChem CID: 11519069
  ChEBI ID: CHEBI:79040
  CAS Number: 869113-09-7
  TTD ID: D09ZOQ
  INTEDE ID: DR1659

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Muscarinic acetylcholine receptor (CHRM)	TTOXS3C	NOUNIPROTAC	Antagonist	[3], [1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6) Main DME	DECB0K3	CP2D6_HUMAN	Substrate	[4]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [3] Clinical pipeline report, company report or official report of GlaxoSmithKline.
• [4] The combination of umeclidinium bromide and vilanterol in the management of chronic obstructive pulmonary disease: current evidence and future prospects. Ther Adv Respir Dis. 2013 Dec;7(6):311-9.
• [5] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [6] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [7] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
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• [12] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [13] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [14] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [15] Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.
• [16] 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.
• [17] 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.
• [18] Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.
• [19] 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.
• [20] 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.
• [21] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [22] The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors. Neuroscience. 2009 May 5;160(2):255-63.
• [23] 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.
• [24] Long-acting bronchodilators in COPD: Where are we now and where are we going Breathe 06/2014; 10(2):110-120.