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	[5]
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[6]
Serotonin	DMOFCRY	Discovery agent	N.A.	Investigative	[7]
5-CT	DM260KD	Discovery agent	N.A.	Investigative	[8]
TFMPP	DMAC8TP	Discovery agent	N.A.	Investigative	[9]
5,6-dichloro-3,4-dihydroquinazolin-2-amine	DMN1S35	Discovery agent	N.A.	Investigative	[10]
MPDT	DMYX31S	Discovery agent	N.A.	Investigative	[11]
5-chloro-3,4-dihydroquinazolin-2-amine	DMKEFJ0	Discovery agent	N.A.	Investigative	[10]
EDMT	DMS3AXK	Discovery agent	N.A.	Investigative	[11]
5-chloro-4-methyl-3,4-dihydroquinazolin-2-amine	DM7FZU2	Discovery agent	N.A.	Investigative	[10]

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	[12]
SB-742457	DM6L4ZT	Alzheimer disease	8A20	Phase 3	[13]
AVN 211	DMVB4OS	Schizophrenia	6A20	Phase 2/3	[14]
SYN120	DMDF7XB	Parkinson disease	8A00.0	Phase 2	[15]
AVN 101	DMJFLBC	Alzheimer disease	8A20	Phase 2	[14]
SYN-120	DMPW0UL	Alzheimer disease	8A20	Phase 2	[16]
PF-05212377	DMPVQYR	Alzheimer disease	8A20	Phase 2	[17]
AVN 322	DMK2LGM	Cognitive impairment	6D71	Phase 2	[13]
SAM-531	DMHVJZ6	Alzheimer disease	8A20	Phase 2	[18]
SUVN-502	DMQD753	Alzheimer disease	8A20	Phase 2	[19]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[20]
JNJ-18038683	DMV1T59	Major depressive disorder	6A70.3	Phase 2	[21]
AVN-101	DMOGFNI	Cognitive impairment	6D71	Phase 2	[22]
ATI-9242	DM6GKMU	Schizophrenia	6A20	Phase 1	[23]
PMID30124346-Compound-34TABLE4	DM2G3VE	Attention deficit hyperactivity disorder	6A05.Z	Patented	[24]
PMID30124346-Compound-13TABLE4	DMHTJVA	Attention deficit hyperactivity disorder	6A05.Z	Patented	[24]
Carbamide derivative 2	DMW5GI3	N. A.	N. A.	Patented	[25]
4-oxadiazole derivative 1	DMWFHKR	N. A.	N. A.	Patented	[25]
SB-269970	DM8WTGA	Sleep-wake disorder	7A00-7B2Z	Terminated	[26]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[27]

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]

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: 89).
• [2] Higher-end serotonin receptors: 5-HT(5), 5-HT(6), and 5-HT(7). J Med Chem. 2003 Jul 3;46(14):2795-812.
• [3] 5-Cyclic amine-3-arylsulfonylindazoles as novel 5-HT6 receptor antagonists. J Med Chem. 2010 Mar 25;53(6):2521-7.
• [4] Novel quinazolinone derivatives as 5-HT7 receptor ligands. Bioorg Med Chem. 2008 Mar 1;16(5):2570-8.
• [5] Cloning and characterisation of the human 5-HT5A serotonin receptor. FEBS Lett. 1994 Dec 5;355(3):242-6.
• [6] Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.
• [7] Identification of a potent, selective, and orally active leukotriene a4 hydrolase inhibitor with anti-inflammatory activity. J Med Chem. 2008 Jul 24;51(14):4150-69.
• [8] Expression of functional mouse 5-HT5A serotonin receptor in the methylotrophic yeast Pichia pastoris: pharmacological characterization and localization. FEBS Lett. 1995 Dec 27;377(3):451-6.
• [9] Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization. Mol Pharmacol. 1993 Mar;43(3):313-9.
• [10] Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: structure-activity relationship elucidation. Bioorg Med Chem Lett. 2008 Jan 1;18(1):256-61.
• [11] 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem. 2000 Mar 9;43(5):1011-8.
• [12] Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. Int J Neuropsychopharmacol. 2010 Sep;13(8):1021-33.
• [13] 5-HT6 receptors and Alzheimer's disease. Alzheimers Res Ther. 2013; 5(2): 15.
• [14] Latrepirdine, a potential novel treatment for Alzheimer's disease and Huntington's chorea. Curr Opin Investig Drugs. 2010 January; 11(1): 80-91.
• [15] Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs. Nat Rev Drug Discov. 2018 Nov;17(11):804-822.
• [16] The Serotonin-6 Receptor as a Novel Therapeutic Target. Exp Neurobiol. 2011 December; 20(4): 159-168.
• [17] PF-05212377 Alzheimer's Disease (Phase 2). Pfizer.
• [18] Activation of 5-HT6 receptors modulates sleep-wake activity and hippocampal theta oscillation. ACS Chem Neurosci. 2013 Jan 16;4(1):191-9.
• [19] 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.
• [20] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [21] 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.
• [22] AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders. J Alzheimers Dis. 2016 May 25;53(2):583-620.
• [23] Pharmacological characteristics of ATI-9242, a Novel Atypical Antipsychotic. FASEB J, April, 2010, 24(Meeting Abstract Supplement),773.12.
• [24] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [25] Acyltransferase inhibitors: a patent review (2010-present).Expert Opin Ther Pat. 2015 Feb;25(2):145-58.
• [26] [(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors. Br J Pharmacol. 2000 May;130(2):409-17.
• [27] 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.