Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT1M8OW)

• DTT Name: Glutamate receptor ionotropic NMDA 2C (GluN2C)
• Synonyms: NR2C; NMDAR2C; N-methyl D-aspartate receptor subtype 2C; Glutamate receptor ionotropic, NMDA 2C; Glutamate [NMDA] receptor subunit epsilon-3; GluN2C
• Gene Name: GRIN2C
• DTT Type: Literature-reported target; [1]
• UniProt ID: NMDE3_HUMAN
• TTD ID: T72595
• Sequence:
  MGGALGPALLLTSLFGAWAGLGPGQGEQGMTVAVVFSSSGPPQAQFRARLTPQSFLDLPL
  EIQPLTVGVNTTNPSSLLTQICGLLGAAHVHGIVFEDNVDTEAVAQILDFISSQTHVPIL
  SISGGSAVVLTPKEPGSAFLQLGVSLEQQLQVLFKVLEEYDWSAFAVITSLHPGHALFLE
  GVRAVADASHVSWRLLDVVTLELGPGGPRARTQRLLRQLDAPVFVAYCSREEAEVLFAEA
  AQAGLVGPGHVWLVPNLALGSTDAPPATFPVGLISVVTESWRLSLRQKVRDGVAILALGA
  HSYWRQHGTLPAPAGDCRVHPGPVSPAREAFYRHLLNVTWEGRDFSFSPGGYLVQPTMVV
  IALNRHRLWEMVGRWEHGVLYMKYPVWPRYSASLQPVVDSRHLTVATLEERPFVIVESPD
  PGTGGCVPNTVPCRRQSNHTFSSGDVAPYTKLCCKGFCIDILKKLARVVKFSYDLYLVTN
  GKHGKRVRGVWNGMIGEVYYKRADMAIGSLTINEERSEIVDFSVPFVETGISVMVARSNG
  TVSPSAFLEPYSPAVWVMMFVMCLTVVAITVFMFEYFSPVSYNQNLTRGKKSGGPAFTIG
  KSVWLLWALVFNNSVPIENPRGTTSKIMVLVWAFFAVIFLASYTANLAAFMIQEQYIDTV
  SGLSDKKFQRPQDQYPPFRFGTVPNGSTERNIRSNYRDMHTHMVKFNQRSVEDALTSLKM
  GKLDAFIYDAAVLNYMAGKDEGCKLVTIGSGKVFATTGYGIAMQKDSHWKRAIDLALLQF
  LGDGETQKLETVWLSGICQNEKNEVMSSKLDIDNMAGVFYMLLVAMGLALLVFAWEHLVY
  WKLRHSVPNSSQLDFLLAFSRGIYSCFSGVQSLASPPRQASPDLTASSAQASVLKMLQAA
  RDMVTTAGVSSSLDRATRTIENWGGGRRAPPPSPCPTPRSGPSPCLPTPDPPPEPSPTGW
  GPPDGGRAALVRRAPQPPGRPPTPGPPLSDVSRVSRRPAWEARWPVRTGHCGRHLSASER
  PLSPARCHYSSFPRADRSGRPFLPLFPELEDLPLLGPEQLARREALLHAAWARGSRPRHA
  SLPSSVAEAFARPSSLPAGCTGPACARPDGHSACRRLAQAQSMCLPIYREACQEGEQAGA
  PAWQHRQHVCLHAHAHLPFCWGAVCPHLPPCASHGSWLSGAWGPLGHRGRTLGLGTGYRD
  SGGLDEISRVARGTQGFPGPCTWRRISSLESEV
• 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 (Probable). Plays a role in regulating the balance between excitatory and inhibitory activity of pyramidal neurons in the prefrontal cortex. Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity).
• 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:
  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]

17 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]
UBP141	DM6IG5J	Discovery agent	N.A.	Investigative	[3]
[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: 458).
• [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] 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.