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

General Information of Drug (ID: DMLDWCB)

• Drug Name: RPR-118723 Drug Info
• Synonyms: RPR-118723; CHEMBL80649

Indication

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

• Cross-matching ID:
  PubChem CID: 9796571
  TTD Drug ID: DMLDWCB

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	Allergic rhinitis	CA08.0	Approved	[2]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[3]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[4]
SPERMINE	DMD4BFY	N. A.	N. A.	Terminated	[5]
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[6]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[7]
DIZOCILPINE	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[8]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[1]
L-698532	DMO9HM7	Neurological disorder	6B60	Terminated	[9]
L-695902	DMT1DNS	N. A.	N. A.	Terminated	[7]

Drug(s) Targeting Glutamate receptor AMPA 1 (GRIA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
E-2007	DMJDYNQ	Diabetic neuropathy	8C0Z	Approved	[10]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[11]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[12]
Farampator	DM76GRQ	Major depressive disorder	6A70.3	Discontinued in Phase 1	[13]
GYKI-52466	DM3YG5P	Alzheimer disease	8A20	Terminated	[14]
GYKI-53655	DMC0JN8	N. A.	N. A.	Terminated	[15]
Zonampanel	DM70HZD	N. A.	N. A.	Terminated	[12]
SORETOLIDE	DMTDLHG	Convulsion	8A68.Z	Terminated	[16]
[3H]kainate	DMMK7XU	Discovery agent	N.A.	Investigative	[17]
DNQX	DMQXPA5	Discovery agent	N.A.	Investigative	[18]

Drug(s) Targeting Glutamate receptor AMPA (GRIA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Halothane	DM80OZ5	Anaesthesia	9A78.6	Approved	[19]
E-2007	DMJDYNQ	Diabetic neuropathy	8C0Z	Approved	[20]
Zopiclone	DMPI6Z0	Insomnia	7A00-7A0Z	Approved	[21]
Sevoflurane	DMC9O43	Anaesthesia	9A78.6	Approved	[22]
Enflurane	DM0YJSB	Anaesthesia	9A78.6	Approved	[23]
Isoflurane	DMY6T31	Anaesthesia	9A78.6	Approved	[24]
Bromazepam	DMY9TCW	Anxiety disorder	6B00-6B0Z	Approved	[25]
Artemisinin SP	DMFETDK	Malaria	1F40-1F45	Approved	[26]
Dihydroergotoxine	DM5D6WZ	Alzheimer disease	8A20	Approved	[27]
Barbiturate	DMJIA6T	Anaesthesia	9A78.6	Approved	[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	[3]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[4]
SPERMINE	DMD4BFY	N. A.	N. A.	Terminated	[5]
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[32]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[7]
DIZOCILPINE	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[8]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[1]

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	[3]
Neu-2000	DMNJTLC	Cardiac arrest	MC82	Phase 1	[38]
EVT100	DMAKWQD	Major depressive disorder	6A70.3	Phase 1	[39]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glutamate receptor AMPA (GRIA)	TTAN6JD	NOUNIPROTAC	Inhibitor	[1]
Glutamate receptor AMPA 1 (GRIA1)	TTVPQTF	GRIA1_HUMAN	Inhibitor	[1]
Glutamate receptor ionotropic NMDA 1 (NMDAR1)	TTLD29N	NMDZ1_HUMAN	Inhibitor	[1]
Glutamate receptor ionotropic NMDA 2A (NMDAR2A)	TTKJEMQ	NMDE1_HUMAN	Inhibitor	[1]
Glutamate receptor ionotropic NMDA 2B (NMDAR2B)	TTN9D8E	NMDE2_HUMAN	Inhibitor	[1]

References

• [1] 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.
• [2] Glycine transport inhibitors for the treatment of schizophrenia: Symptom and disease modification. Curr Opin Drug Discov Devel. 2009 Jul;12(4):468-78.
• [3] 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.
• [4] 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.
• [5] Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents. J Med Chem. 2010 May 13;53(9):3611-7.
• [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: 456).
• [7] 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).
• [8] 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.
• [9] 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.
• [10] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [11] Structural investigation of the 7-chloro-3-hydroxy-1H-quinazoline-2,4-dione scaffold to obtain AMPA and kainate receptor selective antagonists. Syn... J Med Chem. 2006 Oct 5;49(20):6015-26.
• [12] Synthesis and AMPA receptor antagonistic activity of a novel 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acid with a substituted phenyl gr... Bioorg Med Chem Lett. 2004 Oct 18;14(20):5107-11.
• [13] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [14] New 7,8-ethylenedioxy-2,3-benzodiazepines as noncompetitive AMPA receptor antagonists. Bioorg Med Chem Lett. 2006 Jan 1;16(1):167-70.
• [15] Substituted 1,2-dihydrophthalazines: potent, selective, and noncompetitive inhibitors of the AMPA receptor. J Med Chem. 1996 Jan 19;39(2):343-6.
• [16] Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl. 2013;(197):19-24.
• [17] 1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of pot... J Med Chem. 2008 Oct 23;51(20):6614-8.
• [18] Synthesis of chiral 1-(2'-amino-2'-carboxyethyl)-1,4-dihydro-6,7-quinoxaline-2,3-diones: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate recep... J Med Chem. 1996 Oct 25;39(22):4430-8.
• [19] Reduced inhibition of cortical glutamate and GABA release by halothane in mice lacking the K+ channel, TREK-1. Br J Pharmacol. 2007 Nov;152(6):939-45.
• [20] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [21] Eszopiclone: its use in the treatment of insomnia. Neuropsychiatr Dis Treat. 2007 Aug;3(4):441-453.
• [22] Effects of sevoflurane on carrageenan- and fentanyl-induced pain hypersensitivity in Sprague-Dawley rats. Can J Anaesth. 2009 Feb;56(2):126-35.
• [23] Enflurane directly depresses glutamate AMPA and NMDA currents in mouse spinal cord motor neurons independent of actions on GABAA or glycine receptors. Anesthesiology. 2000 Oct;93(4):1075-84.
• [24] Transmembrane residues define the action of isoflurane at the GABAA receptor alpha-3 subunit. Brain Res. 2005 Jan 25;1032(1-2):30-5.
• [25] Glutamatergic and GABAergic modulations of ultrasonic vocalizations during maternal separation distress in mouse pups. Psychopharmacology (Berl). 2009 May;204(1):61-71.
• [26] GABA(A) receptor ligands and their therapeutic potentials. Curr Top Med Chem. 2002 Aug;2(8):817-32.
• [27] Pharmacologic management of Alzheimer disease, Part II: Antioxidants, antihypertensives, and ergoloid derivatives. Ann Pharmacother. 1999 Feb;33(2):188-97.
• [28] Anaesthetic drugs: linking molecular actions to clinical effects. Curr Pharm Des. 2006;12(28):3665-79.
• [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.
• [39] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)