Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Glutamate receptor ionotropic NMDA 2A (NMDAR2A)
• Synonyms: NR2A; NMDA receptor NR2A; N-methyl D-aspartate receptor subtype 2A; HNR2A; Glutamate receptor ionotropic, NMDA 2A; Glutamate [NMDA] receptor subunit epsilon-1; GluN2A
• Gene Name: GRIN2A
• DTT Type: Successful target; [1]
• BioChemical Class: Glutamate-gated ion channel
• UniProt ID: NMDE1_HUMAN
• TTD ID: T22285
• Sequence:
  MGRVGYWTLLVLPALLVWRGPAPSAAAEKGPPALNIAVMLGHSHDVTERELRTLWGPEQA
  AGLPLDVNVVALLMNRTDPKSLITHVCDLMSGARIHGLVFGDDTDQEAVAQMLDFISSHT
  FVPILGIHGGASMIMADKDPTSTFFQFGASIQQQATVMLKIMQDYDWHVFSLVTTIFPGY
  REFISFVKTTVDNSFVGWDMQNVITLDTSFEDAKTQVQLKKIHSSVILLYCSKDEAVLIL
  SEARSLGLTGYDFFWIVPSLVSGNTELIPKEFPSGLISVSYDDWDYSLEARVRDGIGILT
  TAASSMLEKFSYIPEAKASCYGQMERPEVPMHTLHPFMVNVTWDGKDLSFTEEGYQVHPR
  LVVIVLNKDREWEKVGKWENHTLSLRHAVWPRYKSFSDCEPDDNHLSIVTLEEAPFVIVE
  DIDPLTETCVRNTVPCRKFVKINNSTNEGMNVKKCCKGFCIDILKKLSRTVKFTYDLYLV
  TNGKHGKKVNNVWNGMIGEVVYQRAVMAVGSLTINEERSEVVDFSVPFVETGISVMVSRS
  NGTVSPSAFLEPFSASVWVMMFVMLLIVSAIAVFVFEYFSPVGYNRNLAKGKAPHGPSFT
  IGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVWAFFAVIFLASYTANLAAFMIQEEFVD
  QVTGLSDKKFQRPHDYSPPFRFGTVPNGSTERNIRNNYPYMHQYMTKFNQKGVEDALVSL
  KTGKLDAFIYDAAVLNYKAGRDEGCKLVTIGSGYIFATTGYGIALQKGSPWKRQIDLALL
  QFVGDGEMEELETLWLTGICHNEKNEVMSSQLDIDNMAGVFYMLAAAMALSLITFIWEHL
  FYWKLRFCFTGVCSDRPGLLFSISRGIYSCIHGVHIEEKKKSPDFNLTGSQSNMLKLLRS
  AKNISSMSNMNSSRMDSPKRAADFIQRGSLIMDMVSDKGNLMYSDNRSFQGKESIFGDNM
  NELQTFVANRQKDNLNNYVFQGQHPLTLNESNPNTVEVAVSTESKANSRPRQLWKKSVDS
  IRQDSLSQNPVSQRDEATAENRTHSLKSPRYLPEEMAHSDISETSNRATCHREPDNSKNH
  KTKDNFKRSVASKYPKDCSEVERTYLKTKSSSPRDKIYTIDGEKEPGFHLDPPQFVENVT
  LPENVDFPDPYQDPSENFRKGDSTLPMNRNPLHNEEGLSNNDQYKLYSKHFTLKDKGSPH
  SETSERYRQNSTHCRSCLSNMPTYSGHFTMRSPFKCDACLRMGNLYDIDEDQMLQETGNP
  ATGEQVYQQDWAQNNALQLQKNKLRISRQHSYDNIVDKPRELDLSRPSRSISLKDRERLL
  EGNFYGSLFSVPSSKLSGKKSSLFPQGLEDSKRSKSLLPDHTSDNPFLHSHRDDQRLVIG
  RCPSDPYKHSLPSQAVNDSYLRSSLRSTASYCSRDSRGHNDVYISEHVMPYAANKNNMYS
  TPRVLNSCSNRRVYKKMPSIESDV
• 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; channels containing GRIN1 and GRIN2A have higher sensitivity to glutamate and faster kinetics than channels formed by GRIN1 and GRIN2B. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning. 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)
  Dopaminergic synapse (hsa04728)
  Alzheimer's disease (hsa05010)
  Amyotrophic lateral sclerosis (ALS) (hsa05014)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Nicotine addiction (hsa05033)
  Alcoholism (hsa05034)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  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)
  Unblocking of NMDA receptor, glutamate binding and activation (R-HSA-438066)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glycine	DMIOZ29	Allergic rhinitis	CA08.0	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NBQX	DMPHZI5	Neurological disorder	6B60	Phase 1	[2]

11 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	[3]
DIZOCILPINE	DMMGYXR	Cerebrovascular ischaemia	8B1Z	Terminated	[4]
L-687414	DM56VPY	N. A.	N. A.	Terminated	[5]
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[6]
L-695902	DMT1DNS	N. A.	N. A.	Terminated	[5]
L-698532	DMO9HM7	Neurological disorder	6B60	Terminated	[7]
L-698544	DMLRBN1	Alzheimer disease	8A20	Terminated	[5]
L-701324	DMAIJSX	Cerebrovascular ischaemia	8B1Z	Terminated	[7]
MDL-105519	DMHUJCI	N. A.	N. A.	Terminated	[8]
RPR-104632	DM9L50N	N. A.	N. A.	Terminated	[9]
SPERMINE	DMD4BFY	N. A.	N. A.	Terminated	[10]

76 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(+)-HA966	DMKWEAJ	Discovery agent	N.A.	Investigative	[6]
(D)-Ala-Pro-Glu	DMGXTSB	Discovery agent	N.A.	Investigative	[11]
(R)-2-Amino-5-phosphono-pentanoic acid	DMSY4CK	Discovery agent	N.A.	Investigative	[12]
(R)-2-Amino-7-phosphono-heptanoic acid	DM4XEHR	Discovery agent	N.A.	Investigative	[12]
(RS)-(tetrazol-5-yl)glycine	DMYZCRF	Discovery agent	N.A.	Investigative	[6]
1,3-ditolylguanidine	DM04KS1	Discovery agent	N.A.	Investigative	[13]
2-Methylamino-succinic acid(NMDA)	DMKP6BM	Discovery agent	N.A.	Investigative	[6]
3-Benzoyl-7-chloro-4-hydroxy-1H-quinolin-2-one	DMAH4DG	Discovery agent	N.A.	Investigative	[5]
3-Hydroxy-1H-benzo[b]azepine-2,5-dione	DMZSOPU	Discovery agent	N.A.	Investigative	[14]
3-Hydroxy-6-methyl-1H-benzo[b]azepine-2,5-dione	DMYR350	Discovery agent	N.A.	Investigative	[14]
3-Hydroxy-7-nitro-1H-benzo[b]azepine-2,5-dione	DMTEJOY	Discovery agent	N.A.	Investigative	[14]
3-Hydroxy-8-methyl-1H-benzo[b]azepine-2,5-dione	DM7HKIF	Discovery agent	N.A.	Investigative	[14]
3-phenyl-4-hydroxyquinolin-2(1H)-one	DM2C9X8	Discovery agent	N.A.	Investigative	[7]
4,5,7-Trichloro-3-hydroxy-1H-quinolin-2-one	DMXZ9PI	Discovery agent	N.A.	Investigative	[15]
4,6-Dichloro-1H-indole-2-carboxylic acid	DM62XC3	Discovery agent	N.A.	Investigative	[16]
4-Bromo-3-hydroxy-1H-quinolin-2-one	DMYOCFX	Discovery agent	N.A.	Investigative	[15]
4-Bromo-5,7-dichloro-3-hydroxy-1H-quinolin-2-one	DM2QJ5A	Discovery agent	N.A.	Investigative	[15]
4-Chloro-3-hydroxy-1H-quinolin-2-one	DMMALY3	Discovery agent	N.A.	Investigative	[15]
4-hydroxy-5-phenylthieno[2,3-b]pyridin-6(7H)-one	DMT3H2X	Discovery agent	N.A.	Investigative	[7]
4-[2-(4-Phenyl-butylamino)-ethyl]-phenol	DMXLVJW	Discovery agent	N.A.	Investigative	[17]
4-[2-(5-Phenyl-pentylamino)-ethyl]-phenol	DM5J7O8	Discovery agent	N.A.	Investigative	[17]
4-[2-(6-Phenyl-hexylamino)-ethyl]-phenol	DMLCIJX	Discovery agent	N.A.	Investigative	[17]
4-[3-(4-Phenyl-butylamino)-propyl]-phenol	DMOF9YN	Discovery agent	N.A.	Investigative	[17]
4-[3-(5-Phenyl-pentylamino)-propyl]-phenol	DMKDBHN	Discovery agent	N.A.	Investigative	[17]
5,7-Dichloro-3-hydroxy-1H-quinazoline-2,4-dione	DMUADN4	Discovery agent	N.A.	Investigative	[18]
5,7-Dichloro-4-hydroxy-3-phenyl-1H-quinolin-2-one	DMZJKIU	Discovery agent	N.A.	Investigative	[5]
5,7-Dinitro-1,4-dihydro-quinoxaline-2,3-dione	DMG4UCX	Discovery agent	N.A.	Investigative	[5]
6,7-Dichloro-3-hydroxy-1H-quinazoline-2,4-dione	DMNEJ8W	Discovery agent	N.A.	Investigative	[18]
6-Chloro-1,4-dihydro-quinoxaline-2,3-dione	DMURJ34	Discovery agent	N.A.	Investigative	[19]
6-Nitro-1,4-dihydro-quinoxaline-2,3-dione	DM84CTA	Discovery agent	N.A.	Investigative	[19]
7-chloro-3-hydroxyquinazoline-2,4-dione	DM3OMLU	Discovery agent	N.A.	Investigative	[20]
8-Bromo-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DMPVU7H	Discovery agent	N.A.	Investigative	[14]
8-Chloro-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DM842L6	Discovery agent	N.A.	Investigative	[14]
8-Ethyl-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DMY8W0K	Discovery agent	N.A.	Investigative	[14]
8-Fluoro-3-hydroxy-1H-benzo[b]azepine-2,5-dione	DMBZSAO	Discovery agent	N.A.	Investigative	[14]
Ala-Pro-Glu	DMTWB54	Discovery agent	N.A.	Investigative	[11]
AP-7	DMBU942	Discovery agent	N.A.	Investigative	[21]
Benzyl 4-aminobutyl(3-aminopropyl)carbamate	DMOKVAT	Discovery agent	N.A.	Investigative	[22]
CGP61594	DM8KFZH	Discovery agent	N.A.	Investigative	[6]
Conantokin-R	DMN4KJI	Discovery agent	N.A.	Investigative	[23]
d-AP5	DMY5OTN	Discovery agent	N.A.	Investigative	[6]
D-aspartic acid	DM7Z892	Discovery agent	N.A.	Investigative	[6]
d-CCPene	DM36D0F	Discovery agent	N.A.	Investigative	[6]
DNQX	DMQXPA5	Discovery agent	N.A.	Investigative	[24]
Gly-Amp-Glu	DMO8LAC	Discovery agent	N.A.	Investigative	[11]
Gly-b7Pro-Glu	DM8L09J	Discovery agent	N.A.	Investigative	[11]
Gly-Hyp-Glu	DM8XR4Y	Discovery agent	N.A.	Investigative	[11]
Gly-Pip-Glu	DMM0JA4	Discovery agent	N.A.	Investigative	[11]
H-Gly-D-dmP-Glu-OH	DMX2TGD	Discovery agent	N.A.	Investigative	[25]
H-Gly-dmP-Glu-OH	DMOYQPM	Discovery agent	N.A.	Investigative	[25]
homoquinolinic acid	DMBW5DU	Discovery agent	N.A.	Investigative	[6]
L-aspartic acid	DMWGPO6	Hypokalemia	5C77	Investigative	[6]
LY233053	DMC82DA	Discovery agent	N.A.	Investigative	[6]
MDL 100,453	DMLI5VH	Discovery agent	N.A.	Investigative	[26]
N,N'-Bis-(4-butoxy-phenyl)-guanidine	DMLOP2B	Discovery agent	N.A.	Investigative	[13]
N,N'-Bis-(4-butyl-phenyl)-guanidine	DMOS2GH	Discovery agent	N.A.	Investigative	[13]
N,N'-Bis-(4-ethyl-phenyl)-guanidine	DM0CTG7	Discovery agent	N.A.	Investigative	[13]
N,N'-Bis-(4-hexyl-phenyl)-guanidine	DM0RQGU	Discovery agent	N.A.	Investigative	[13]
N,N'-Bis-(4-isopropyl-phenyl)-guanidine	DMM38BC	Discovery agent	N.A.	Investigative	[13]
N,N'-Bis-(4-sec-butyl-phenyl)-guanidine	DMFDXLB	Discovery agent	N.A.	Investigative	[13]
N-(2-methoxybenzyl)cinnamamidine	DM06S5Z	Discovery agent	N.A.	Investigative	[27]
N1-dansyl-spermine	DM76CLF	Discovery agent	N.A.	Investigative	[6]
Nle-Pro-Glu	DM0FA6B	Discovery agent	N.A.	Investigative	[11]
NVP-AAM077	DM9DURZ	Discovery agent	N.A.	Investigative	[28]
Phe-Pro-Glu	DMJMLKA	Discovery agent	N.A.	Investigative	[11]
PHENCYCLIDINE	DMQBEYX	Discovery agent	N.A.	Investigative	[29]
RPR-118723	DMLDWCB	Discovery agent	N.A.	Investigative	[9]
TCN-201	DMMT2GP	Discovery agent	N.A.	Investigative	[30]
Tenocyclidine	DMRM1QV	Discovery agent	N.A.	Investigative	[31]
TRANSTORINE	DMP4T87	Discovery agent	N.A.	Investigative	[16]
UBP141	DM6IG5J	Discovery agent	N.A.	Investigative	[12]
[3H]CGP39653	DMITR7A	Discovery agent	N.A.	Investigative	[6]
[3H]CGS19755	DM7H3JN	Discovery agent	N.A.	Investigative	[6]
[3H]CPP	DMR5UBF	Discovery agent	N.A.	Investigative	[6]
[3H]dizocilpine	DMEC2PF	Discovery agent	N.A.	Investigative	[6]
[3H]MDL105519	DMPKGHB	Discovery agent	N.A.	Investigative	[6]

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	8.43E-01	-0.37	-0.45

References

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