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

General Information of Drug (ID: DMWXLYZ)

Drug Name
Darifenacin Drug Info
Synonyms
Enablex; Emselex; 133099-04-4; UNII-APG9819VLM; UK-88525; APG9819VLM; CHEMBL1346; CHEBI:391960; (S)-1-(2-(2,3-Dihydro-5-benzofuranyl)ethyl)-alpha,alpha-diphenyl-3-pyrrolidineacetamide; 2-[(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl]-2,2-diphenylacetamide; darifenacine; [3H]darifenacin; 2-{(3S)-1-[2-(2,3-dihydro-1-benzofuran-5-yl)ethyl]pyrrolidin-3-yl}-2,2-diphenylacetamide; NCGC00168775-01; Darifenacin (USAN/INN); Darifenacinum; Darifenacina; Darifenacin [USAN:INN:BAN]; Emselex; Emselex (TN); Enablex (TN)
Indication
Disease Entry ICD 11 Status REF
Overactive bladder GC50.0 Approved [1]
Priapism Investigative [2]
Therapeutic Class
Urinary antispasmodics
Cross-matching ID
PubChem CID
444031
ChEBI ID
CHEBI:391960
CAS Number
CAS 133099-04-4
TTD Drug ID
DMWXLYZ
INTEDE Drug ID
DR0417
ACDINA Drug ID
D00169

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DME
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Muscarinic acetylcholine receptor (CHRM)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Acetylcholine DMDF79Z Cataract 9B10 Approved [7]
Tiotropium DMFDC0Q Chronic obstructive pulmonary disease CA22 Approved [8]
Methylscopolamine DM5VWOB Peptic ulcer DA61 Approved [9]
Clidinium DMUMQZ0 Abdominal stomach pain DD91.4 Approved [10]
Oxybutynin hydrochloride DMF2KLU Urinary incontinence MF50.2 Approved [11]
Incruse Ellipta DM32GSJ Chronic obstructive pulmonary disease CA22 Approved [12]
Revefenacin DMMP5SI Chronic obstructive pulmonary disease CA22 Approved [13]
Scopolamine DMOM8AL Addictive disorder 6C50-6C5Z Approved [14]
Isopropamide iodide DMQYV60 Allergic rhinitis CA08.0 Approved [15]
SUN-101 DMXNZQK Chronic obstructive pulmonary disease CA22 Phase 3 [16]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Targeting Muscarinic acetylcholine receptor M3 (CHRM3)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Tolterodine DMSHPW8 Overactive bladder GC50.0 Approved [17]
ACECLIDINE DMOLNCZ Glaucoma/ocular hypertension 9C61 Approved [18]
Tiotropium DMFDC0Q Chronic obstructive pulmonary disease CA22 Approved [19]
Ipratropium DMFQ320 Obstructive lung disease CA22.Z Approved [20]
Methacholine Chloride DMGS4QH Asthma CA23 Approved [21]
SMT-D002 DM1I93C Seborrhea ED91.2 Approved [22]
Solifenacin DMG592Q Overactive bladder GC50.0 Approved [23]
Methylscopolamine DM5VWOB Peptic ulcer DA61 Approved [24]
Cevimeline DMWSMND Sjogren syndrome 4A43.20 Approved [25]
Methscopolamine Bromide DMHP8FI Nausea and vomiting MD90 Approved [26]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [27]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [28]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [29]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [30]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [31]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [32]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [33]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [34]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [28]
Verapamil DMA7PEW Angina pectoris BA40 Approved [35]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By Cytochrome P450 2D6 (CYP2D6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [36]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [37]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [38]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [31]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [35]
Quinine DMSWYF5 Malaria 1F40-1F45 Approved [39]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [40]
Dopamine DMPGUCF Acromegaly 5A60.0 Approved [41]
Nicotine DMWX5CO Lung cancer 2C25.0 Approved [42]
Propranolol DM79NTF Angina pectoris BA40 Approved [43]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Potassium voltage-gated channel subfamily H member 2 (KCNH2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Metoclopramide DMFA5MY Nausea MD90 Approved [44]
Quinidine DMLPICK N. A. N. A. Approved [45]
Verapamil DMA7PEW Angina pectoris BA40 Approved [46]
Erythromycin DM4K7GQ Acne vulgaris ED80 Approved [47]
Clarithromycin DM4M1SG Acute maxillary sinusitis Approved [47]
Disopyramide DM5SYZP Long QT syndrome BC65.0 Approved [48]
Propranolol DM79NTF Angina pectoris BA40 Approved [49]
Amiodarone DMUTEX3 Tachyarrhythmias BC71 Approved [50]
Dofetilide DMPN1TW Sinus rhythm disorder BC9Y Approved [51]
Flecainide DMSQDLE Tachyarrhythmias BC71 Approved [47]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Muscarinic acetylcholine receptor (CHRM) TTOXS3C NOUNIPROTAC Antagonist [3]
Muscarinic acetylcholine receptor M3 (CHRM3) TTQ13Z5 ACM3_HUMAN Antagonist [4]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) Main DME DE4LYSA CP3A4_HUMAN Substrate [5]
Cytochrome P450 2D6 (CYP2D6) Main DME DECB0K3 CP2D6_HUMAN Substrate [5]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Gene/Protein Processing [6]

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: 321).
2 Darifenacin FDA Label
3 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.
4 M(1) and M(3) muscarinic receptors are involved in the release of urinary bladder-derived relaxant factor. Pharmacol Res. 2009 May;59(5):300-5.
5 The clinical pharmacokinetics of darifenacin. Clin Pharmacokinet. 2006;45(4):325-50.
6 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.
7 Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.
8 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.
9 Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.
10 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.
11 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.
12 Clinical pipeline report, company report or official report of GlaxoSmithKline.
13 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
14 The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors. Neuroscience. 2009 May 5;160(2):255-63.
15 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.
16 Long-acting bronchodilators in COPD: Where are we now and where are we going Breathe 06/2014; 10(2):110-120.
17 Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.
18 Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem. 1993 Apr 2;36(7):842-7.
19 DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
20 Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.
21 Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.
22 Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.
23 Comparison of muscarinic receptor selectivity of solifenacin and oxybutynin in the bladder and submandibular gland of muscarinic receptor knockout ... Eur J Pharmacol. 2009 Aug 1;615(1-3):201-6.
24 Interaction of neuromuscular blocking drugs with recombinant human m1-m5 muscarinic receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1998 Nov;125(5):1088-94.
25 Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor ... Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G112-G123.
26 Agonist-regulated alteration of the affinity of pancreatic muscarinic cholinergic receptors. J Biol Chem. 1993 Oct 25;268(30):22436-43.
27 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
28 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
29 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
30 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
31 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
32 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
33 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
34 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
35 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
36 Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
37 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.
38 CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
39 Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
40 Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
41 Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
42 Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
43 Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
44 Comparison of the effects of metoclopramide and domperidone on HERG channels. Pharmacology. 2005 Apr;74(1):31-6. doi: 10.1159/000083234. Epub 2005 Jan 7.
45 Further insights into the effect of quinidine in short QT syndrome caused by a mutation in HERG. J Cardiovasc Electrophysiol. 2005 Jan;16(1):54-8. doi: 10.1046/j.1540-8167.2005.04470.x.
46 Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds. Assay Drug Dev Technol. 2004 Oct;2(5):497-506. doi: 10.1089/adt.2004.2.497.
47 Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
48 Pharmacology of the short QT syndrome N588K-hERG K+ channel mutation: differential impact on selected class I and class III antiarrhythmic drugs. Br J Pharmacol. 2008 Nov;155(6):957-66. doi: 10.1038/bjp.2008.325. Epub 2008 Aug 25.
49 Comparison of HERG channel blocking effects of various beta-blockers-- implication for clinical strategy. Br J Pharmacol. 2006 Mar;147(6):642-52. doi: 10.1038/sj.bjp.0706508.
50 Inhibitory effects of the class III antiarrhythmic drug amiodarone on cloned HERG potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1999 Mar;359(3):212-9. doi: 10.1007/pl00005344.
51 Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation. FEBS Lett. 2000 May 26;474(1):111-5. doi: 10.1016/s0014-5793(00)01586-6.