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

General Information of Drug (ID: DMO4GBK)

• Drug Name: vinburnine Drug Info
• Synonyms: eburnamonine

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 71203
  ChEBI ID: CHEBI:4740
  CAS Number: CAS 4880-88-0
  TTD Drug ID: DMO4GBK

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	[4]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[5]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[6]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[7]
Clidinium	DMUMQZ0	Abdominal stomach pain	DD91.4	Approved	[8]
Oxybutynin hydrochloride	DMF2KLU	Urinary incontinence	MF50.2	Approved	[9]
Incruse Ellipta	DM32GSJ	Chronic obstructive pulmonary disease	CA22	Approved	[10]
Revefenacin	DMMP5SI	Chronic obstructive pulmonary disease	CA22	Approved	[11]
Scopolamine	DMOM8AL	Addictive disorder	6C50-6C5Z	Approved	[12]
Isopropamide iodide	DMQYV60	Allergic rhinitis	CA08.0	Approved	[13]

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	[14]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[15]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[16]
Ipratropium	DMFQ320	Obstructive lung disease	CA22.Z	Approved	[17]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[18]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[19]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[20]
Solifenacin	DMG592Q	Overactive bladder	GC50.0	Approved	[21]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[22]
Cevimeline	DMWSMND	Sjogren syndrome	4A43.20	Approved	[23]

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	[24]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[25]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[26]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[27]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[27]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[28]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[29]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[30]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[31]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[27]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Muscarinic acetylcholine receptor (CHRM)	TTOXS3C	NOUNIPROTAC	Modulator (allosteric modulator)	[2]
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Modulator (allosteric modulator)	[2]

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	[3]

References

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• [2] Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol. 1997 Jul;52(1):172-9.
• [3] 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.
• [4] Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. Mol Pharmacol. 2004 Jan;65(1):257-66.
• [5] 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.
• [6] 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.
• [7] Lithocholylcholine, a bile acid/acetylcholine hybrid, is a muscarinic receptor antagonist. J Pharmacol Exp Ther. 2002 Oct;303(1):29-35.
• [8] 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.
• [9] 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.
• [10] Clinical pipeline report, company report or official report of GlaxoSmithKline.
• [11] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [12] The amygdala modulates morphine-induced state-dependent memory retrieval via muscarinic acetylcholine receptors. Neuroscience. 2009 May 5;160(2):255-63.
• [13] 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.
• [14] Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.
• [15] 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.
• [16] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [17] Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.
• [18] 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.
• [19] Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.
• [20] Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] 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.
• [30] 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.
• [31] 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.