Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5POTG)

• DTT Name: Glutamate receptor ionotropic NMDA 2D (GluN2D)
• Synonyms: NR2D; NMDAR2D; N-methyl D-aspartate receptor subtype 2D; Glutamate receptor ionotropic, NMDA 2D; Glutamate [NMDA] receptor subunit epsilon-4; GluN2D; EB11
• Gene Name: GRIN2D
• DTT Type: Literature-reported target; [1]
• UniProt ID: NMDE4_HUMAN
• TTD ID: T56588
• Sequence:
  MRGAGGPRGPRGPAKMLLLLALACASPFPEEAPGPGGAGGPGGGLGGARPLNVALVFSGP
  AYAAEAARLGPAVAAAVRSPGLDVRPVALVLNGSDPRSLVLQLCDLLSGLRVHGVVFEDD
  SRAPAVAPILDFLSAQTSLPIVAVHGGAALVLTPKEKGSTFLQLGSSTEQQLQVIFEVLE
  EYDWTSFVAVTTRAPGHRAFLSYIEVLTDGSLVGWEHRGALTLDPGAGEAVLSAQLRSVS
  AQIRLLFCAREEAEPVFRAAEEAGLTGSGYVWFMVGPQLAGGGGSGAPGEPPLLPGGAPL
  PAGLFAVRSAGWRDDLARRVAAGVAVVARGAQALLRDYGFLPELGHDCRAQNRTHRGESL
  HRYFMNITWDNRDYSFNEDGFLVNPSLVVISLTRDRTWEVVGSWEQQTLRLKYPLWSRYG
  RFLQPVDDTQHLTVATLEERPFVIVEPADPISGTCIRDSVPCRSQLNRTHSPPPDAPRPE
  KRCCKGFCIDILKRLAHTIGFSYDLYLVTNGKHGKKIDGVWNGMIGEVFYQRADMAIGSL
  TINEERSEIVDFSVPFVETGISVMVARSNGTVSPSAFLEPYSPAVWVMMFVMCLTVVAVT
  VFIFEYLSPVGYNRSLATGKRPGGSTFTIGKSIWLLWALVFNNSVPVENPRGTTSKIMVL
  VWAFFAVIFLASYTANLAAFMIQEEYVDTVSGLSDRKFQRPQEQYPPLKFGTVPNGSTEK
  NIRSNYPDMHSYMVRYNQPRVEEALTQLKAGKLDAFIYDAAVLNYMARKDEGCKLVTIGS
  GKVFATTGYGIALHKGSRWKRPIDLALLQFLGDDEIEMLERLWLSGICHNDKIEVMSSKL
  DIDNMAGVFYMLLVAMGLSLLVFAWEHLVYWRLRHCLGPTHRMDFLLAFSRGMYSCCSAE
  AAPPPAKPPPPPQPLPSPAYPAPRPAPGPAPFVPRERASVDRWRRTKGAGPPGGAGLADG
  FHRYYGPIEPQGLGLGLGEARAAPRGAAGRPLSPPAAQPPQKPPPSYFAIVRDKEPAEPP
  AGAFPGFPSPPAPPAAAATAVGPPLCRLAFEDESPPAPARWPRSDPESQPLLGPGAGGAG
  GTGGAGGGAPAAPPPCRAAPPPCPYLDLEPSPSDSEDSESLGGASLGGLEPWWFADFPYP
  YAERLGPPPGRYWSVDKLGGWRAGSWDYLPPRSGPAAWHCRHCASLELLPPPRHLSCSHD
  GLDGGWWAPPPPPWAAGPLPRRRARCGCPRSHPHRPRASHRTPAAAAPHHHRHRRAAGGW
  DLPPPAPTSRSLEDLSSCPRAAPARRLTGPSRHARRCPHAAHWGPPLPTASHRRHRGGDL
  GTRRGSAHFSSLESEV
• Function: Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. 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.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Circadian entrainment (hsa04713)
  Long-term potentiation (hsa04720)
  Glutamatergic synapse (hsa04724)
  Alzheimer disease (hsa05010)
  Amyotrophic lateral sclerosis (hsa05014)
  Spinocerebellar ataxia (hsa05017)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Cocaine addiction (hsa05030)
  Amphetamine addiction (hsa05031)
  Nicotine addiction (hsa05033)
  Alcoholism (hsa05034)
• Reactome Pathway:
  Ras activation upon Ca2+ influx through NMDA receptor (R-HSA-442982)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Neurexins and neuroligins (R-HSA-6794361)
  Synaptic adhesion-like molecules (R-HSA-8849932)
  Assembly and cell surface presentation of NMDA receptors (R-HSA-9609736)
  Negative regulation of NMDA receptor-mediated neuronal transmission (R-HSA-9617324)
  Long-term potentiation (R-HSA-9620244)
  Unblocking of NMDA receptors, glutamate binding and activation (R-HSA-438066)

Molecular Interaction Atlas (MIA) of This DTT

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-689560	DMCVY4U	Neurodegenerative disorder	8A20-8A23	Terminated	[1]

18 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(RS)-(tetrazol-5-yl)glycine	DMYZCRF	Discovery agent	N.A.	Investigative	[1]
2-Methylamino-succinic acid(NMDA)	DMKP6BM	Discovery agent	N.A.	Investigative	[1]
CGP61594	DM8KFZH	Discovery agent	N.A.	Investigative	[1]
d-AP5	DMY5OTN	Discovery agent	N.A.	Investigative	[1]
D-aspartic acid	DM7Z892	Discovery agent	N.A.	Investigative	[1]
d-CCPene	DM36D0F	Discovery agent	N.A.	Investigative	[1]
DQP-1105	DMQLJ3Y	Discovery agent	N.A.	Investigative	[2]
homoquinolinic acid	DMBW5DU	Discovery agent	N.A.	Investigative	[1]
L-aspartic acid	DMWGPO6	Hypokalemia	5C77	Investigative	[1]
LY233053	DMC82DA	Discovery agent	N.A.	Investigative	[1]
N1-dansyl-spermine	DM76CLF	Discovery agent	N.A.	Investigative	[1]
QNZ 46	DM01RZX	Discovery agent	N.A.	Investigative	[3]
UBP141	DM6IG5J	Discovery agent	N.A.	Investigative	[4]
[3H]CGP39653	DMITR7A	Discovery agent	N.A.	Investigative	[1]
[3H]CGS19755	DM7H3JN	Discovery agent	N.A.	Investigative	[1]
[3H]CPP	DMR5UBF	Discovery agent	N.A.	Investigative	[1]
[3H]dizocilpine	DMEC2PF	Discovery agent	N.A.	Investigative	[1]
[3H]MDL105519	DMPKGHB	Discovery agent	N.A.	Investigative	[1]

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. (Target id: 459).
• [2] Mechanism for noncompetitive inhibition by novel GluN2C/D N-methyl-D-aspartate receptor subunit-selective modulators. Mol Pharmacol. 2011 Nov;80(5):782-95.
• [3] Structural and mechanistic determinants of a novel site for noncompetitive inhibition of GluN2D-containing NMDA receptors. J Neurosci. 2011 Mar 9;31(10):3650-61.
• [4] Synthesis and pharmacology of N1-substituted piperazine-2,3-dicarboxylic acid derivatives acting as NMDA receptor antagonists. J Med Chem. 2005 Apr 7;48(7):2627-37.