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

General Information of Drug (ID: DM04KS1)

• Drug Name: 1,3-ditolylguanidine Drug Info
• Synonyms: 1,3-Di-o-tolylguanidine; 97-39-2; Di-o-tolylguanidine; DOTG; Vulkacite DOTG; 1,3-Ditolylguanidine; Vulkacit DOTG; Eveite DOTG; ditolylguanidine; Vulkacit dotg/C; Nocceler DT; Sanceler DT; DOTG accelerator; Soxinol DT; Akrochem DOTG; Vulcafor DOTG; 1,3-Bis(o-tolyl)guanidine; Guanidine, N,N'-bis(2-methylphenyl)-; Diorthotolylguanidine; 1,3-Di-o-tolyguanidine; N,N'-Di-o-tolylguanidine; Guanidine, 1,3-di-o-tolyl-; USAF A-6598; NSC 473; CNS 1001; N,N'-Di-o-tolueylguanidine; UNII-LL2P01I17O; 1,3-di-(2-tolyl)guanidine; NSC 132023; [3H]-di-o-tolylguanidine; DITOLYLGUANIDINE

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1] , [2] , [3]

• Cross-matching ID:
  PubChem CID: 7333
  ChEBI ID: CHEBI:92585
  CAS Number: CAS 97-39-2
  TTD Drug ID: DM04KS1

Molecule-Related Drug Atlas

Drug(s) Targeting Glutamate receptor ionotropic NMDA 2A (NMDAR2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glycine	DMIOZ29	Malnutrition	5B50-5B71	Approved	[7]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[8]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[9]
Spermine	DMD4BFY	N. A.	N. A.	Terminated	[10]
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[11]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[12]
Dizocilpine	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[13]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[14]
L-698532	DMO9HM7	Neurological disorder	6B60	Terminated	[15]
L-695902	DMT1DNS	N. A.	N. A.	Terminated	[12]

Drug(s) Targeting Sigma intracellular receptor 2 (TMEM97)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MIN-101	DMCJY35	Schizophrenia	6A20	Phase 3	[16]
CT1812	DMBRKZ7	Alzheimer disease	8A20	Phase 2	[17]
Isoindoline derivative 5	DMIUTQW	N. A.	N. A.	Patented	[18]
Isoindoline derivative 3	DM2MYL9	N. A.	N. A.	Patented	[18]
Isoindoline derivative 4	DMP1NKI	N. A.	N. A.	Patented	[18]
Isoindoline derivative 2	DMTE0S3	N. A.	N. A.	Patented	[18]
Isoindoline derivative 1	DMD19QC	N. A.	N. A.	Patented	[18]
Benzamide derivative 9	DMVFSJZ	N. A.	N. A.	Patented	[18]
Benzamide derivative 10	DM9PKU2	N. A.	N. A.	Patented	[18]
PMID30185082-Compound-57	DMNDF1Z	N. A.	N. A.	Patented	[18]

Drug(s) Targeting Opioid receptor sigma 1 (OPRS1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dextromethorphan	DMUDJZM	Cough	MD12	Approved	[19]
Dextromethorphan polistirex	DMEHCY5	Dry cough	MD12	Approved	[20]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[21]
AVP-786	DMV1SOR	Alzheimer disease	8A20	Phase 3	[22]
ADX N05	DMLBYRA	Mood disorder	6A60-6E23	Phase 3	[23]
Igmesine	DMH97XA	Major depressive disorder	6A70.3	Phase 2	[24]
OPC-14523	DMB1WF3	Bulimia nervosa	6B81	Phase 2	[25]
ANAVEX 2-73	DM67OU4	Alzheimer disease	8A20	Phase 1	[26]
SSR-125047	DMSUFW6	Schizophrenia	6A20	Phase 1	[27]
SA-5845	DM6XZRL	Central nervous system disease	8A04-8D87	Phase 1	[28]

Drug(s) Targeting Glutamate receptor ionotropic NMDA 1 (NMDAR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cycloserine	DMT1I52	Bacterial infection	1A00-1C4Z	Approved	[29]
D-Serine	DM3YH4I	N. A.	N. A.	Phase 4	[30]
ELIPRODIL	DMIOGZM	Multiple sclerosis	8A40	Phase 2	[31]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[8]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[9]
Spermine	DMD4BFY	N. A.	N. A.	Terminated	[10]
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[32]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[12]
Dizocilpine	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[13]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[14]

Drug(s) Targeting Glutamate receptor ionotropic NMDA 2B (NMDAR2B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alpha 1-PI	DMXC1K9	Alpha-1 antitrypsin deficiency	5C5A	Approved	[33]
ELIPRODIL	DMIOGZM	Multiple sclerosis	8A40	Phase 2	[31]
CP-101,606	DMIU19E	Parkinson disease	8A00.0	Phase 2	[34]
CERC-301	DMSABRI	Major depressive disorder	6A70.3	Phase 2	[35]
RGH-896	DMCHZAN	Peripheral neuropathy	8C0Z	Phase 2	[36]
MIJ821	DMN45RI	Major depressive disorder	6A70.3	Phase 2	[37]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[8]
Neu-2000	DMNJTLC	Cardiac arrest	MC82	Phase 1	[38]
EVT100	DMAKWQD	Major depressive disorder	6A70.3	Phase 1	[16]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[9]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glutamate receptor ionotropic NMDA 1 (NMDAR1)	TTLD29N	NMDZ1_HUMAN	Inhibitor	[3]
Glutamate receptor ionotropic NMDA 2A (NMDAR2A)	TTKJEMQ	NMDE1_HUMAN	Inhibitor	[3]
Glutamate receptor ionotropic NMDA 2B (NMDAR2B)	TTN9D8E	NMDE2_HUMAN	Inhibitor	[3]
Opioid receptor sigma 1 (OPRS1)	TT5TPI6	SGMR1_HUMAN	Agonist	[4] , [5]
Sigma intracellular receptor 2 (TMEM97)	TT9NXW4	SGMR2_HUMAN	Agonist	[6] , [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: 6685).
• [2] 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: 6684).
• [3] Synthesis and pharmacological evaluation of N,N'-diarylguanidines as potent sodium channel blockers and anticonvulsant agents. J Med Chem. 1998 Aug 13;41(17):3298-302.
• [4] Sigma1 and sigma2 receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503. Synapse. 2006 May;59(6):350-8.
• [5] Synthesis and characterization of [125I]-N-(N-benzylpiperidin-4-yl)-4- iodobenzamide, a new sigma receptor radiopharmaceutical: high-affinity bindi... J Med Chem. 1994 Jun 10;37(12):1737-9.
• [6] 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. (Target id: 2553).
• [7] Glycine transport inhibitors for the treatment of schizophrenia: Symptom and disease modification. Curr Opin Drug Discov Devel. 2009 Jul;12(4):468-78.
• [8] Synthesis, ionotropic glutamate receptor binding affinity, and structure-activity relationships of a new set of 4,5-dihydro-8-heteroaryl-4-oxo-1,2,... J Med Chem. 2001 Sep 13;44(19):3157-65.
• [9] 4,10-Dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acid derivatives: highly potent and selective AMPA receptors antagonists with... Bioorg Med Chem Lett. 2000 May 15;10(10):1133-7.
• [10] Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents. J Med Chem. 2010 May 13;53(9):3611-7.
• [11] 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. (Target id: 456).
• [12] Amino acid bioisosteres: design of 2-quinolone derivatives as glycine-site N-methyl-D-aspartate receptor antagonists, Bioorg. Med. Chem. Lett. 3(2):299-304 (1993).
• [13] Synthesis and evaluation of 6,11-ethanohexahydrobenzo[b]quinolizidines: a new class of noncompetitive N-methyl-D-aspartate antagonists. J Med Chem. 1995 Jun 23;38(13):2483-9.
• [14] Indeno[1,2-b]pyrazin-2,3-diones: a new class of antagonists at the glycine site of the NMDA receptor with potent in vivo activity. J Med Chem. 2000 Jun 15;43(12):2371-81.
• [15] Synthesis of thieno[2,3-b]pyridinones acting as cytoprotectants and as inhibitors of [3H]glycine binding to the N-methyl-D-aspartate (NMDA) receptor. J Med Chem. 2006 Feb 9;49(3):864-71.
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [18] The sigma-2 (-2) receptor: a review of recent patent applications: 2013-2018.Expert Opin Ther Pat. 2018 Sep;28(9):655-663.
• [19] Dextromethorphan/quinidine: AVP 923, dextromethorphan/cytochrome P450-2D6 inhibitor, quinidine/dextromethorphan. Drugs R D. 2005;6(3):174-7.
• [20] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [21] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [22] Antitussives and substance abuse. Subst Abuse Rehabil. 2013 Nov 6;4:75-82.
• [23] Clinical pipeline report, company report or official report of SK BioPhamaceuticals.
• [24] Antiamnesic and neuroprotective effects of donepezil against learning impairments induced in mice by exposure to carbon monoxide gas. J Pharmacol Exp Ther. 2006 Jun;317(3):1307-19.
• [25] Antidepressant-like responses to the combined sigma and 5-HT1A receptor agonist OPC-14523. Neuropharmacology. 2001 Dec;41(8):976-88.
• [26] 2011 Pipeline of Anavex.
• [27] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [28] Tumor imaging with 2 sigma-receptor ligands, 18F-FE-SA5845 and 11C-SA4503: a feasibility study. J Nucl Med. 2004 Nov;45(11):1939-45.
• [29] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [30] Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
• [31] 4-Hydroxy-1-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piperidine: a novel, potent, and selective NR1/2B NMDA receptor antagonist. J Med Chem. 1999 Jul 29;42(15):2993-3000.
• [32] 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. (Target id: 455).
• [33] NMDA receptor stimulation induces reversible fission of the neuronal endoplasmic reticulum. PLoS One. 2009;4(4):e5250.
• [34] NMDA receptors as targets for drug action in neuropathic pain. Eur J Pharmacol. 2001 Oct 19;429(1-3):71-8.
• [35] Inhibition of in vivo [(3)H]MK-801 binding by NMDA receptor open channel blockers and GluN2B antagonists in rats and mice. Eur J Pharmacol. 2015 Nov 5;766:1-8.
• [36] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [37] Clinical pipeline report, company report or official report of Cadent Therapeutics.
• [38] Neu2000, an NR2B-selective, moderate NMDA receptor antagonist and potent spin trapping molecule for stroke. Drug News Perspect. 2010 Nov;23(9):549-56.