Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLD29N)

• DTT Name: Glutamate receptor ionotropic NMDA 1 (NMDAR1)
• Synonyms: NmethylDaspartate receptor subunit NR1; NMDR1; NMD-R1; N-methyl-D-aspartate receptor subunit NR1; Glutamate receptor ionotropic, NMDA 1; Glutamate [NMDA] receptor subunit zeta1; Glutamate [NMDA] receptor subunit zeta-1; GluN1
• Gene Name: GRIN1
• DTT Type: Successful target; [1]
• BioChemical Class: Glutamate-gated ion channel
• UniProt ID: NMDZ1_HUMAN
• TTD ID: T62276
• Sequence:
  MSTMRLLTLALLFSCSVARAACDPKIVNIGAVLSTRKHEQMFREAVNQANKRHGSWKIQL
  NATSVTHKPNAIQMALSVCEDLISSQVYAILVSHPPTPNDHFTPTPVSYTAGFYRIPVLG
  LTTRMSIYSDKSIHLSFLRTVPPYSHQSSVWFEMMRVYSWNHIILLVSDDHEGRAAQKRL
  ETLLEERESKAEKVLQFDPGTKNVTALLMEAKELEARVIILSASEDDAATVYRAAAMLNM
  TGSGYVWLVGEREISGNALRYAPDGILGLQLINGKNESAHISDAVGVVAQAVHELLEKEN
  ITDPPRGCVGNTNIWKTGPLFKRVLMSSKYADGVTGRVEFNEDGDRKFANYSIMNLQNRK
  LVQVGIYNGTHVIPNDRKIIWPGGETEKPRGYQMSTRLKIVTIHQEPFVYVKPTLSDGTC
  KEEFTVNGDPVKKVICTGPNDTSPGSPRHTVPQCCYGFCIDLLIKLARTMNFTYEVHLVA
  DGKFGTQERVNNSNKKEWNGMMGELLSGQADMIVAPLTINNERAQYIEFSKPFKYQGLTI
  LVKKEIPRSTLDSFMQPFQSTLWLLVGLSVHVVAVMLYLLDRFSPFGRFKVNSEEEEEDA
  LTLSSAMWFSWGVLLNSGIGEGAPRSFSARILGMVWAGFAMIIVASYTANLAAFLVLDRP
  EERITGINDPRLRNPSDKFIYATVKQSSVDIYFRRQVELSTMYRHMEKHNYESAAEAIQA
  VRDNKLHAFIWDSAVLEFEASQKCDLVTTGELFFRSGFGIGMRKDSPWKQNVSLSILKSH
  ENGFMEDLDKTWVRYQECDSRSNAPATLTFENMAGVFMLVAGGIVAGIFLIFIEIAYKRH
  KDARRKQMQLAFAAVNVWRKNLQDRKSGRAEPDPKKKATFRAITSTLASSFKRRRSSKDT
  STGGGRGALQNQKDTVLPRRAIEREEGQLQLCSRHRES
• Function: Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition. Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium.
• KEGG Pathway:
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Calcium signaling pathway (hsa04020)
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Circadian entrainment (hsa04713)
  Long-term potentiation (hsa04720)
  Glutamatergic synapse (hsa04724)
  Alzheimer's disease (hsa05010)
  Amyotrophic lateral sclerosis (ALS) (hsa05014)
  Huntington's disease (hsa05016)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Nicotine addiction (hsa05033)
  Alcoholism (hsa05034)
• Reactome Pathway:
  Unblocking of NMDA receptor, glutamate binding and activation (R-HSA-438066)
  CREB phosphorylation through the activation of CaMKII (R-HSA-442729)
  Ras activation uopn Ca2+ infux through NMDA receptor (R-HSA-442982)
  RAF/MAP kinase cascade (R-HSA-5673001)
  EPHB-mediated forward signaling (R-HSA-3928662)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cycloserine	DMT1I52	Bacterial infection	1A00-1C4Z	Approved	[1]
D-Serine	DM3YH4I	N. A.	N. A.	Phase 4	[2]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ELIPRODIL	DMIOGZM	Multiple sclerosis	8A40	Phase 2	[3]
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[4]

12 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
YM-90K	DMWRT4L	Convulsion	8A68.Z	Discontinued in Phase 2	[5]
AM-92016	DMMZNSC	N. A.	N. A.	Terminated	[6]
DIZOCILPINE	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[7]
L-687414	DM56VPY	N. A.	N. A.	Terminated	[8]
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[9]
L-695902	DMT1DNS	N. A.	N. A.	Terminated	[8]
L-698532	DMO9HM7	Neurological disorder	6B60	Terminated	[10]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[8]
L-701324	DMAIJSX	Cerebrovascular ischaemia	8B1Z	Terminated	[10]
MDL-105519	DMHUJCI	N. A.	N. A.	Terminated	[11]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[12]
SPERMINE	DMD4BFY	N. A.	N. A.	Terminated	[13]

90 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-HA966	DMKWEAJ	Discovery agent	N.A.	Investigative	[9]
(D)-Ala-Pro-Glu	DMGXTSB	Discovery agent	N.A.	Investigative	[14]
(R)-2-Amino-5-phosphono-pentanoic acid	DMSY4CK	Discovery agent	N.A.	Investigative	[15]
(R)-2-Amino-7-phosphono-heptanoic acid	DM4XEHR	Discovery agent	N.A.	Investigative	[15]
(RS)-(tetrazol-5-yl)glycine	DMYZCRF	Discovery agent	N.A.	Investigative	[9]
1,3-ditolylguanidine	DM04KS1	Discovery agent	N.A.	Investigative	[16]
2-(4-Phenoxy-benzyl)-1H-benzoimidazole	DM65IF1	Discovery agent	N.A.	Investigative	[17]
2-(4-Phenoxy-benzyl)-3H-benzoimidazol-4-ol	DM3HANW	Discovery agent	N.A.	Investigative	[17]
2-(4-Phenoxy-benzyl)-3H-benzoimidazol-5-ol	DMFO19B	Discovery agent	N.A.	Investigative	[17]
2-(4-Phenoxy-benzyl)-3H-benzoimidazol-5-ylamine	DMJSBFU	Discovery agent	N.A.	Investigative	[17]
2-Methylamino-succinic acid(NMDA)	DMKP6BM	Discovery agent	N.A.	Investigative	[9]
2-Pyridin-4-yl-1,2,3,4-tetrahydro-isoquinoline	DM5D09Q	Discovery agent	N.A.	Investigative	[18]
3-Benzoyl-7-chloro-4-hydroxy-1H-quinolin-2-one	DMAH4DG	Discovery agent	N.A.	Investigative	[8]
3-Carbamoyl-6-chloro-1H-indole-2-carboxylic acid	DMP6TLY	Discovery agent	N.A.	Investigative	[19]
3-Hydroxy-1H-benzo[b]azepine-2,5-dione	DMZSOPU	Discovery agent	N.A.	Investigative	[20]
3-Hydroxy-6-methyl-1H-benzo[b]azepine-2,5-dione	DMYR350	Discovery agent	N.A.	Investigative	[20]
3-Hydroxy-7-nitro-1H-benzo[b]azepine-2,5-dione	DMTEJOY	Discovery agent	N.A.	Investigative	[20]
3-Hydroxy-8-methyl-1H-benzo[b]azepine-2,5-dione	DM7HKIF	Discovery agent	N.A.	Investigative	[20]
3-phenyl-4-hydroxyquinolin-2(1H)-one	DM2C9X8	Discovery agent	N.A.	Investigative	[10]
4,5,7-Trichloro-3-hydroxy-1H-quinolin-2-one	DMXZ9PI	Discovery agent	N.A.	Investigative	[21]
4,6-Dichloro-1H-indole-2-carboxylic acid	DM62XC3	Discovery agent	N.A.	Investigative	[22]
4-(3,4-Dihydro-1H-isoquinolin-2-yl)-quinoline	DMCOJIL	Discovery agent	N.A.	Investigative	[18]
4-Benzyl-1-(2-phenoxy-ethyl)-piperidine	DMQZ0D6	Discovery agent	N.A.	Investigative	[3]
4-Benzyl-1-phenethyl-piperidine hydrochloride	DMAI6X2	Discovery agent	N.A.	Investigative	[23]
4-Bromo-3-hydroxy-1H-quinolin-2-one	DMYOCFX	Discovery agent	N.A.	Investigative	[21]
4-Bromo-5,7-dichloro-3-hydroxy-1H-quinolin-2-one	DM2QJ5A	Discovery agent	N.A.	Investigative	[21]
4-Chloro-3-hydroxy-1H-quinolin-2-one	DMMALY3	Discovery agent	N.A.	Investigative	[21]
4-hydroxy-5-phenylthieno[2,3-b]pyridin-6(7H)-one	DMT3H2X	Discovery agent	N.A.	Investigative	[10]
4-[2-(3-Phenyl-propylamino)-ethyl]-phenol	DM64WSV	Discovery agent	N.A.	Investigative	[23]
4-[2-(4-Benzyl-piperidin-1-yl)-ethoxy]-phenol	DM74G6Q	Discovery agent	N.A.	Investigative	[3]
4-[2-(4-Phenyl-butoxy)-ethyl]-phenol	DML8B3T	Discovery agent	N.A.	Investigative	[23]
4-[2-(4-Phenyl-butylamino)-ethyl]-phenol	DMXLVJW	Discovery agent	N.A.	Investigative	[23]
4-[2-(4-Phenyl-piperidin-1-yl)-ethoxy]-phenol	DM8JM4Q	Discovery agent	N.A.	Investigative	[3]
4-[2-(5-Phenyl-pentylamino)-ethyl]-phenol	DM5J7O8	Discovery agent	N.A.	Investigative	[23]
4-[2-(6-Phenyl-hexylamino)-ethyl]-phenol	DMLCIJX	Discovery agent	N.A.	Investigative	[23]
4-[3-(4-Phenyl-butylamino)-propyl]-phenol	DMOF9YN	Discovery agent	N.A.	Investigative	[24]
4-[3-(5-Phenyl-pentylamino)-propyl]-phenol	DMKDBHN	Discovery agent	N.A.	Investigative	[23]
4-{2-[Ethyl-(4-phenyl-butyl)-amino]-ethyl}-phenol	DMA21GM	Discovery agent	N.A.	Investigative	[23]
5,6,7-Trichloro-1,4-dihydro-quinoxaline-2,3-dione	DMTL4S9	Discovery agent	N.A.	Investigative	[25]
5,7-Dibromo-1,4-dihydro-quinoxaline-2,3-dione	DMA50BQ	Discovery agent	N.A.	Investigative	[25]
5,7-Dichloro-1,4-dihydro-quinoxaline-2,3-dione	DMOJ5LM	Discovery agent	N.A.	Investigative	[25]
5,7-Dichloro-3-hydroxy-1H-quinazoline-2,4-dione	DMUADN4	Discovery agent	N.A.	Investigative	[26]
5,7-Dichloro-4-hydroxy-3-phenyl-1H-quinolin-2-one	DMZJKIU	Discovery agent	N.A.	Investigative	[8]
5,7-Dichlorokynurenic Acid	DMHKQ1L	Discovery agent	N.A.	Investigative	[27]
5,7-Dinitro-1,4-dihydro-quinoxaline-2,3-dione	DMG4UCX	Discovery agent	N.A.	Investigative	[8]
6,7-Dichloro-1,4-dihydro-quinoxaline-2,3-dione	DMMX1QJ	Discovery agent	N.A.	Investigative	[25]
6,7-Dichloro-3-hydroxy-1H-quinazoline-2,4-dione	DMNEJ8W	Discovery agent	N.A.	Investigative	[26]
6-Chloro-1,4-dihydro-quinoxaline-2,3-dione	DMURJ34	Discovery agent	N.A.	Investigative	[28]
6-Methoxy-2-(4-phenoxy-benzyl)-1H-benzoimidazole	DMZP3XJ	Discovery agent	N.A.	Investigative	[17]
6-Nitro-1,4-dihydro-quinoxaline-2,3-dione	DM84CTA	Discovery agent	N.A.	Investigative	[28]
6-Nitro-2-(4-phenoxy-benzyl)-1H-benzoimidazole	DMZTXDV	Discovery agent	N.A.	Investigative	[17]
7-chloro-3-hydroxyquinazoline-2,4-dione	DM3OMLU	Discovery agent	N.A.	Investigative	[29]
8-Bromo-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DMPVU7H	Discovery agent	N.A.	Investigative	[20]
8-Chloro-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DM842L6	Discovery agent	N.A.	Investigative	[20]
8-Ethyl-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DMY8W0K	Discovery agent	N.A.	Investigative	[20]
8-Fluoro-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DMBZSAO	Discovery agent	N.A.	Investigative	[20]
Ala-Pro-Glu	DMTWB54	Discovery agent	N.A.	Investigative	[14]
AP-7	DMBU942	Discovery agent	N.A.	Investigative	[30]
Benzyl 4-aminobutyl(3-aminopropyl)carbamate	DMOKVAT	Discovery agent	N.A.	Investigative	[31]
CGP61594	DM8KFZH	Discovery agent	N.A.	Investigative	[9]
Cycloleucine	DM0L6E1	Discovery agent	N.A.	Investigative	[32]
D-aspartic acid	DM7Z892	Discovery agent	N.A.	Investigative	[9]
DNQX	DMQXPA5	Discovery agent	N.A.	Investigative	[33]
Gly-Amp-Glu	DMO8LAC	Discovery agent	N.A.	Investigative	[14]
Gly-b7Pro-Glu	DM8L09J	Discovery agent	N.A.	Investigative	[14]
Gly-Hyp-Glu	DM8XR4Y	Discovery agent	N.A.	Investigative	[14]
Gly-Pip-Glu	DMM0JA4	Discovery agent	N.A.	Investigative	[14]
H-Gly-D-dmP-Glu-OH	DMX2TGD	Discovery agent	N.A.	Investigative	[34]
H-Gly-dmP-Glu-OH	DMOYQPM	Discovery agent	N.A.	Investigative	[34]
homoquinolinic acid	DMBW5DU	Discovery agent	N.A.	Investigative	[9]
L-aspartic acid	DMWGPO6	Hypokalemia	5C77	Investigative	[9]
N,N'-Bis-(4-butoxy-phenyl)-guanidine	DMLOP2B	Discovery agent	N.A.	Investigative	[16]
N,N'-Bis-(4-butyl-phenyl)-guanidine	DMOS2GH	Discovery agent	N.A.	Investigative	[16]
N,N'-Bis-(4-ethyl-phenyl)-guanidine	DM0CTG7	Discovery agent	N.A.	Investigative	[16]
N,N'-Bis-(4-hexyl-phenyl)-guanidine	DM0RQGU	Discovery agent	N.A.	Investigative	[16]
N,N'-Bis-(4-isopropyl-phenyl)-guanidine	DMM38BC	Discovery agent	N.A.	Investigative	[16]
N,N'-Bis-(4-sec-butyl-phenyl)-guanidine	DMFDXLB	Discovery agent	N.A.	Investigative	[16]
N-(2-methoxybenzyl)cinnamamidine	DM06S5Z	Discovery agent	N.A.	Investigative	[35]
Nle-Pro-Glu	DM0FA6B	Discovery agent	N.A.	Investigative	[14]
Phe-Pro-Glu	DMJMLKA	Discovery agent	N.A.	Investigative	[14]
PHENCYCLIDINE	DMQBEYX	Discovery agent	N.A.	Investigative	[36]
Phenethyl-(3-phenyl-propyl)-amine	DMQWFO1	Discovery agent	N.A.	Investigative	[23]
Phenethyl-(4-phenyl-butyl)-amine	DMFQMHK	Discovery agent	N.A.	Investigative	[23]
RPR-118723	DMLDWCB	Discovery agent	N.A.	Investigative	[12]
TRANSTORINE	DMP4T87	Discovery agent	N.A.	Investigative	[22]
[3H]CGP39653	DMITR7A	Discovery agent	N.A.	Investigative	[9]
[3H]CGS19755	DM7H3JN	Discovery agent	N.A.	Investigative	[9]
[3H]CPP	DMR5UBF	Discovery agent	N.A.	Investigative	[9]
[3H]dizocilpine	DMEC2PF	Discovery agent	N.A.	Investigative	[9]
[3H]MDL105519	DMPKGHB	Discovery agent	N.A.	Investigative	[9]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Parkinson's disease	8A00.0	Substantia nigra tissue	1.12E-01	-0.5	-1.8

References

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