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

General Information of Drug (ID: DMMC0I7)

• Drug Name: METHIOTHEPIN Drug Info
• Synonyms: methiothepin; Metitepine; Methiothepine; Metitepinum; Metitepina; Metitepine [INN]; Metitepinum [INN-Latin]; Metitepina [INN-Spanish]; BRN 0626221; 20229-30-5; (+-)-10-(4-Methylpiperazinyl)-8-(methylthio)-10,11-dihydrodibenzo(b,f)thiepin; (+-)-8-Methylthio-10-(4-methylpiperazino)-10,11-dihydrodibenzo(b,f)thiepin; (+-)-1-(10,11-Dihydro-8-(methylthio)dibenzo(b,f)thiepin-10-yl)-4-methylpiperazine; CHEBI:64203; 1-(10,11-Dihydro-8-(methylthio)dibenzo(b,f)thiepin-10-yl)-4-methylpiperazine; NCGC00024665-03; DSSTox_CID_24000

Indication

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

• Cross-matching ID:
  PubChem CID: 4106
  ChEBI ID: CHEBI:64203
  CAS Number: CAS 20229-30-5
  TTD Drug ID: DMMC0I7

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 5A receptor (HTR5A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[6]
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[7]
SEROTONIN	DMOFCRY	Discovery agent	N.A.	Investigative	[8]
5-CT	DM260KD	Discovery agent	N.A.	Investigative	[9]
TFMPP	DMAC8TP	Discovery agent	N.A.	Investigative	[10]
5,6-dichloro-3,4-dihydroquinazolin-2-amine	DMN1S35	Discovery agent	N.A.	Investigative	[11]
MPDT	DMYX31S	Discovery agent	N.A.	Investigative	[12]
5-chloro-3,4-dihydroquinazolin-2-amine	DMKEFJ0	Discovery agent	N.A.	Investigative	[11]
EDMT	DMS3AXK	Discovery agent	N.A.	Investigative	[12]
5-chloro-4-methyl-3,4-dihydroquinazolin-2-amine	DM7FZU2	Discovery agent	N.A.	Investigative	[11]

Drug(s) Targeting 5-HT 6 receptor (HTR6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LU AE58054	DMWGRQD	Schizophrenia	6A20	Phase 3	[13]
SB-742457	DM6L4ZT	Alzheimer disease	8A20	Phase 3	[14]
AVN 211	DMVB4OS	Schizophrenia	6A20	Phase 2/3	[15]
SYN120	DMDF7XB	Parkinson disease	8A00.0	Phase 2	[16]
AVN 101	DMJFLBC	Alzheimer disease	8A20	Phase 2	[15]
SYN-120	DMPW0UL	Alzheimer disease	8A20	Phase 2	[17]
PF-05212377	DMPVQYR	Alzheimer disease	8A20	Phase 2	[18]
AVN 322	DMK2LGM	Cognitive impairment	6D71	Phase 2	[14]
SAM-531	DMHVJZ6	Alzheimer disease	8A20	Phase 2	[19]
SUVN-502	DMQD753	Alzheimer disease	8A20	Phase 2	[20]

Drug(s) Targeting 5-HT 7 receptor (HTR7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[21]
JNJ-18038683	DMV1T59	Major depressive disorder	6A70.3	Phase 2	[22]
AVN-101	DMOGFNI	Cognitive impairment	6D71	Phase 2	[23]
ATI-9242	DM6GKMU	Schizophrenia	6A20	Phase 1	[24]
PMID30124346-Compound-34TABLE4	DM2G3VE	Attention deficit hyperactivity disorder	6A05.Z	Patented	[25]
PMID30124346-Compound-13TABLE4	DMHTJVA	Attention deficit hyperactivity disorder	6A05.Z	Patented	[25]
Carbamide derivative 2	DMW5GI3	N. A.	N. A.	Patented	[26]
4-oxadiazole derivative 1	DMWFHKR	N. A.	N. A.	Patented	[26]
SB-269970	DM8WTGA	Sleep-wake disorder	7A00-7B2Z	Terminated	[27]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[28]

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	[29]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[30]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[31]
Erythromycin	DM4K7GQ	Acne vulgaris	ED80	Approved	[32]
Clarithromycin	DM4M1SG	Acute maxillary sinusitis		Approved	[32]
Disopyramide	DM5SYZP	Long QT syndrome	BC65.0	Approved	[33]
Propranolol	DM79NTF	Angina pectoris	BA40	Approved	[34]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[35]
Dofetilide	DMPN1TW	Sinus rhythm disorder	BC9Y	Approved	[36]
Flecainide	DMSQDLE	Tachyarrhythmias	BC71	Approved	[32]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 5A receptor (HTR5A)	TTRUFDT	5HT5A_HUMAN	Inhibitor	[2]
5-HT 6 receptor (HTR6)	TTJS8PY	5HT6R_HUMAN	Inhibitor	[3]
5-HT 7 receptor (HTR7)	TTO9X1H	5HT7R_HUMAN	Inhibitor	[4]

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	[5]

References

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• [18] PF-05212377 Alzheimer's Disease (Phase 2). Pfizer.
• [19] Activation of 5-HT6 receptors modulates sleep-wake activity and hippocampal theta oscillation. ACS Chem Neurosci. 2013 Jan 16;4(1):191-9.
• [20] Novel and Potent 5-Piperazinyl Methyl-N1-aryl Sulfonyl Indole Derivatives as 5-HT6 Receptor Ligands. ACS Med Chem Lett. 2010 October 14; 1(7): 340-344.
• [21] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [22] Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity. Front Behav Neurosci. 2015 Jan 15;8:453.
• [23] AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders. J Alzheimers Dis. 2016 May 25;53(2):583-620.
• [24] Pharmacological characteristics of ATI-9242, a Novel Atypical Antipsychotic. FASEB J, April, 2010, 24(Meeting Abstract Supplement),773.12.
• [25] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [26] Acyltransferase inhibitors: a patent review (2010-present).Expert Opin Ther Pat. 2015 Feb;25(2):145-58.
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• [28] Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
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• [30] 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.
• [31] 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.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] 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.
• [36] 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.