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

General Information of Drug (ID: DMCVY4U)

• Drug Name: L-689560 Drug Info
• Synonyms: trans-2-Carboxy-5,7-dichloro-4-(((phenylamino)carbonyl)amino)-1,2,3,4-tetrahydroquinoline; C17H15Cl2N3O3; L 689560; L-689,560; 4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline; 139051-78-8; (2S,4R)-5,7-dichloro-4-(phenylcarbamoylamino)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid; 2-Quinolinecarboxylic acid, 5,7-dichloro-1,2,3,4-tetrahydro-4-(((phenylamino)carbonyl)amino)-, trans-(+-)-; [3H]L689560; AC1L3TN7; SCHEMBL193615; GTPL4239; GTPL4086; ZINC2567729; compound 35

Indication

Disease Entry	ICD 11	Status	REF
Neurodegenerative disorder	8A20-8A23	Terminated	[1] , [2]

• Cross-matching ID:
  PubChem CID: 121918
  CAS Number: CAS 139051-78-8
  TTD Drug ID: DMCVY4U

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	[9]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[10]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[11]
Spermine	DMD4BFY	N. A.	N. A.	Terminated	[12]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[13]
Dizocilpine	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[14]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[15]
L-698532	DMO9HM7	Neurological disorder	6B60	Terminated	[16]
L-695902	DMT1DNS	N. A.	N. A.	Terminated	[13]
L-701324	DMAIJSX	Cerebrovascular ischaemia	8B1Z	Terminated	[16]

Drug(s) Targeting Glutamate receptor ionotropic NMDA 2D (GluN2D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
D-aspartic acid	DM7Z892	Discovery agent	N.A.	Investigative	[7]
[3H]CPP	DMR5UBF	Discovery agent	N.A.	Investigative	[7]
2-Methylamino-succinic acid(NMDA)	DMKP6BM	Discovery agent	N.A.	Investigative	[7]
[3H]MDL105519	DMPKGHB	Discovery agent	N.A.	Investigative	[7]
[3H]CGP39653	DMITR7A	Discovery agent	N.A.	Investigative	[7]
homoquinolinic acid	DMBW5DU	Discovery agent	N.A.	Investigative	[7]
[3H]dizocilpine	DMEC2PF	Discovery agent	N.A.	Investigative	[7]
CGP61594	DM8KFZH	Discovery agent	N.A.	Investigative	[7]
(RS)-(tetrazol-5-yl)glycine	DMYZCRF	Discovery agent	N.A.	Investigative	[7]
[3H]CGS19755	DM7H3JN	Discovery agent	N.A.	Investigative	[7]

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	[17]
D-Serine	DM3YH4I	N. A.	N. A.	Phase 4	[18]
ELIPRODIL	DMIOGZM	Multiple sclerosis	8A40	Phase 2	[19]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[10]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[11]
Spermine	DMD4BFY	N. A.	N. A.	Terminated	[12]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[13]
Dizocilpine	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[14]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[15]
L-698532	DMO9HM7	Neurological disorder	6B60	Terminated	[16]

Drug(s) Targeting N-methyl-D-aspartate receptor (NMDAR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-glutamic acid	DM4PUDW	Schizophrenia	6A20	Approved	[20]
Cycloserine	DMT1I52	Bacterial infection	1A00-1C4Z	Approved	[21]
Benzphetamine	DMIJATC	Obesity	5B81	Approved	[22]
Ketamine	DMT5HA4	Anaesthesia	9A78.6	Approved	[23]
Felbamate	DM1V5ZS	Epilepsy	8A60-8A68	Approved	[24]
Memantine	DMD9WSC	Alzheimer disease	8A20	Approved	[25]
Huperzine A	DMMAWLU	Alzheimer disease	8A20	Approved	[26]
Levorphanol	DMGS80V	Pain	MG30-MG3Z	Approved	[27]
Magnesium Sulfate	DMVEK07	Acute pain	MG31	Approved	[28]
Magnesium	DMU4ORS	Ischemic stroke	8B11.5Z	Approved	[29]

Drug(s) Targeting Glutamate receptor ionotropic NMDA 2C (GluN2C)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
D-aspartic acid	DM7Z892	Discovery agent	N.A.	Investigative	[6]
[3H]CPP	DMR5UBF	Discovery agent	N.A.	Investigative	[6]
2-Methylamino-succinic acid(NMDA)	DMKP6BM	Discovery agent	N.A.	Investigative	[6]
[3H]MDL105519	DMPKGHB	Discovery agent	N.A.	Investigative	[6]
[3H]CGP39653	DMITR7A	Discovery agent	N.A.	Investigative	[6]
homoquinolinic acid	DMBW5DU	Discovery agent	N.A.	Investigative	[6]
[3H]dizocilpine	DMEC2PF	Discovery agent	N.A.	Investigative	[6]
CGP61594	DM8KFZH	Discovery agent	N.A.	Investigative	[6]
(RS)-(tetrazol-5-yl)glycine	DMYZCRF	Discovery agent	N.A.	Investigative	[6]
[3H]CGS19755	DM7H3JN	Discovery agent	N.A.	Investigative	[6]

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	[30]
ELIPRODIL	DMIOGZM	Multiple sclerosis	8A40	Phase 2	[19]
CP-101,606	DMIU19E	Parkinson disease	8A00.0	Phase 2	[31]
CERC-301	DMSABRI	Major depressive disorder	6A70.3	Phase 2	[32]
RGH-896	DMCHZAN	Peripheral neuropathy	8C0Z	Phase 2	[33]
MIJ821	DMN45RI	Major depressive disorder	6A70.3	Phase 2	[34]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[10]
Neu-2000	DMNJTLC	Cardiac arrest	MC82	Phase 1	[35]
EVT100	DMAKWQD	Major depressive disorder	6A70.3	Phase 1	[36]
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[11]

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	Antagonist	[3]
Glutamate receptor ionotropic NMDA 2A (NMDAR2A)	TTKJEMQ	NMDE1_HUMAN	Antagonist	[4]
Glutamate receptor ionotropic NMDA 2B (NMDAR2B)	TTN9D8E	NMDE2_HUMAN	Antagonist	[5]
Glutamate receptor ionotropic NMDA 2C (GluN2C)	TT1M8OW	NMDE3_HUMAN	Antagonist	[6]
Glutamate receptor ionotropic NMDA 2D (GluN2D)	TT5POTG	NMDE4_HUMAN	Antagonist	[7]
N-methyl-D-aspartate receptor (NMDAR)	TT9IK2Z	NOUNIPROTAC	Modulator	[8]

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: 4239).
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001828)
• [3] 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).
• [4] 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).
• [5] 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: 457).
• [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: 458).
• [7] 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: 459).
• [8] Characterization of the binding of [3H]L-689,560, an antagonist for the glycine site on the N-methyl-D-aspartate receptor, to rat brain membranes. Mol Pharmacol. 1992 May;41(5):923-30.
• [9] Glycine transport inhibitors for the treatment of schizophrenia: Symptom and disease modification. Curr Opin Drug Discov Devel. 2009 Jul;12(4):468-78.
• [10] 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.
• [11] 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.
• [12] Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents. J Med Chem. 2010 May 13;53(9):3611-7.
• [13] 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).
• [14] 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.
• [15] 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.
• [16] 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.
• [17] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [18] Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
• [19] 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.
• [20] Altered expression of genes involved in GABAergic transmission and neuromodulation of granule cell activity in the cerebellum of schizophrenia pati... Am J Psychiatry. 2008 Dec;165(12):1594-603.
• [21] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [22] Amphetamine inhibits the N-methyl-D-aspartate receptor-mediated responses by directly interacting with the receptor/channel complex. J Pharmacol Exp Ther. 2002 Mar;300(3):1008-16.
• [23] Ketamine modulates theta and gamma oscillations. J Cogn Neurosci. 2010 Jul;22(7):1452-64.
• [24] Molecular determinants of the anticonvulsant felbamate binding site in the N-methyl-D-aspartate receptor. J Med Chem. 2008 Mar 27;51(6):1534-45.
• [25] The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence. Int J Geriatr Psychiatry. 2003 Sep;18(Suppl 1):S23-32.
• [26] Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res. 2009 Jan;83(1):1-43.
• [27] Neuroprotective agents for the treatment of acute ischemic stroke. Curr Neurol Neurosci Rep. 2003 Jan;3(1):9-20.
• [28] Magnesium sulfate diminishes the effects of amide local anesthetics in rat sciatic-nerve block. Reg Anesth Pain Med. 2007 Jul-Aug;32(4):288-95.
• [29] Emerging drugs for acute ischemic stroke. Expert Opin Emerg Drugs. 2009 Mar;14(1):33-42.
• [30] NMDA receptor stimulation induces reversible fission of the neuronal endoplasmic reticulum. PLoS One. 2009;4(4):e5250.
• [31] NMDA receptors as targets for drug action in neuropathic pain. Eur J Pharmacol. 2001 Oct 19;429(1-3):71-8.
• [32] 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.
• [33] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [34] Clinical pipeline report, company report or official report of Cadent Therapeutics.
• [35] Neu2000, an NR2B-selective, moderate NMDA receptor antagonist and potent spin trapping molecule for stroke. Drug News Perspect. 2010 Nov;23(9):549-56.
• [36] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)