Target Information

Target General Infomation
Target ID
T76414
Former ID
TTDC00299
Target Name
Glutamate [NMDA] receptor subunit epsilon 2
Gene Name
GRIN2B
Synonyms
Glutamate receptor NR2B subunit; HNR3; N-methyl-D-aspartate receptor subunit 3; N-methylD-aspartate receptor subtype 2B; NMDA NR2B receptor; NMDA receptor NR2B; NMDA receptor subunit 2B; NMDAR2B; NR2B; NR3; GRIN2B
Target Type
Clinical Trial
Disease Brain injury [ICD10: S09.90]
Cardiac arrest [ICD10: I46]
Cancer pain [ICD9: 140-229, 338,780; ICD10: R52, G89]
Cerebrovascular ischaemia [ICD9: 434.91; ICD10: I61-I63]
Convulsions [ICD9: 780.3; ICD10: R56.0]
Diabetic peripheral neuropathic pain [ICD9: 250.6, 338,780; ICD10: E10.4, E11.4, E13.4, R52, G89]
Major depressive disorder [ICD9: 296.2, 296.3, 710.0; ICD10: F32, F33, M32]
Multiple scierosis [ICD9: 340; ICD10: G35]
Neuropathic pain [ICD9: 356.0, 356.8; ICD10: G64, G90.0]
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89]
Parkinson's disease [ICD9: 332; ICD10: G20]
Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity).
BioChemical Class
Glutamate-gated ion channel
Target Validation
T76414
UniProt ID
Q13224
Sequence
MKPRAECCSPKFWLVLAVLAVSGSRARSQKSPPSIGIAVILVGTSDEVAIKDAHEKDDFH
HLSVVPRVELVAMNETDPKSIITRICDLMSDRKIQGVVFADDTDQEAIAQILDFISAQTL
TPILGIHGGSSMIMADKDESSMFFQFGPSIEQQASVMLNIMEEYDWYIFSIVTTYFPGYQ
DFVNKIRSTIENSFVGWELEEVLLLDMSLDDGDSKIQNQLKKLQSPIILLYCTKEEATYI
FEVANSVGLTGYGYTWIVPSLVAGDTDTVPAEFPTGLISVSYDEWDYGLPARVRDGIAII
TTAASDMLSEHSFIPEPKSSCYNTHEKRIYQSNMLNRYLINVTFEGRNLSFSEDGYQMHP
KLVIILLNKERKWERVGKWKDKSLQMKYYVWPRMCPETEEQEDDHLSIVTLEEAPFVIVE
SVDPLSGTCMRNTVPCQKRIVTENKTDEEPGYIKKCCKGFCIDILKKISKSVKFTYDLYL
VTNGKHGKKINGTWNGMIGEVVMKRAYMAVGSLTINEERSEVVDFSVPFIETGISVMVSR
SNGTVSPSAFLEPFSADVWVMMFVMLLIVSAVAVFVFEYFSPVGYNRCLADGREPGGPSF
TIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVWAFFAVIFLASYTANLAAFMIQEEYV
DQVSGLSDKKFQRPNDFSPPFRFGTVPNGSTERNIRNNYAEMHAYMGKFNQRGVDDALLS
LKTGKLDAFIYDAAVLNYMAGRDEGCKLVTIGSGKVFASTGYGIAIQKDSGWKRQVDLAI
LQLFGDGEMEELEALWLTGICHNEKNEVMSSQLDIDNMAGVFYMLGAAMALSLITFICEH
LFYWQFRHCFMGVCSGKPGMVFSISRGIYSCIHGVAIEERQSVMNSPTATMNNTHSNILR
LLRTAKNMANLSGVNGSPQSALDFIRRESSVYDISEHRRSFTHSDCKSYNNPPCEENLFS
DYISEVERTFGNLQLKDSNVYQDHYHHHHRPHSIGSASSIDGLYDCDNPPFTTQSRSISK
KPLDIGLPSSKHSQLSDLYGKFSFKSDRYSGHDDLIRSDVSDISTHTVTYGNIEGNAAKR
RKQQYKDSLKKRPASAKSRREFDEIELAYRRRPPRSPDHKRYFRDKEGLRDFYLDQFRTK
ENSPHWEHVDLTDIYKERSDDFKRDSVSGGGPCTNRSHIKHGTGDKHGVVSGVPAPWEKN
LTNVEWEDRSGGNFCRSCPSKLHNYSTTVTGQNSGRQACIRCEACKKAGNLYDISEDNSL
QELDQPAAPVAVTSNASTTKYPQSPTNSKAQKKNRNKLRRQHSYDTFVDLQKEEAALAPR
SVSLKDKGRFMDGSPYAHMFEMSAGESTFANNKSSVPTAGHHHHNNPGGGYMLSKSLYPD
RVTQNPFIPTFGDDQCLLHGSKSYFFRQPTVAGASKARPDFRALVTNKPVVSALHGAVPA
RFQKDICIGNQSNPCVPNNKNPRAFNGSSNGHVYEKLSSIESDV
Drugs and Mode of Action
Drug(s) CERC-301 Drug Info Phase 2 Major depressive disorder [1]
CP-101,606 Drug Info Phase 2 Parkinson's disease [2]
ELIPRODIL Drug Info Phase 2 Multiple scierosis [3]
RGH-896 Drug Info Phase 2 Diabetic peripheral neuropathic pain [4]
NBQX Drug Info Phase 1 Neurological disease [5]
Neu-2000 Drug Info Phase 1 Cardiac arrest [6]
Ifenprodil Drug Info Withdrawn from market Cancer pain [7], [8]
EVT-101 Drug Info Discontinued in Phase 2 Neuropathic pain [9]
YM-90K Drug Info Discontinued in Phase 2 Convulsions [10]
Besonprodil Drug Info Discontinued in Phase 1 Parkinson's disease [11]
EVT-103 Drug Info Discontinued in Phase 1 Major depressive disorder [12]
DIZOCILPINE Drug Info Terminated Cerebrovascular ischaemia [13], [14]
L-687414 Drug Info Terminated Discovery agent [15]
L-695902 Drug Info Terminated Discovery agent [16]
L-698532 Drug Info Terminated Neurological disease [17]
L-701324 Drug Info Terminated Cerebrovascular ischaemia [18], [19], [20]
MDL-105519 Drug Info Terminated Discovery agent [21]
RO-25-6981 Drug Info Terminated Cancer pain [22]
RPR-104632 Drug Info Terminated Discovery agent [23]
Agonist (+)-HA966 Drug Info [24]
(RS)-(tetrazol-5-yl)glycine Drug Info [24]
D-aspartic acid Drug Info [24]
homoquinolinic acid Drug Info [24]
L-aspartic acid Drug Info [24]
NMDA Drug Info [24]
[3H]glycine Drug Info [24]
Inhibitor (D)-Ala-Pro-Glu Drug Info [25]
(R)-2-Amino-5-phosphono-pentanoic acid Drug Info [26]
(R)-2-Amino-7-phosphono-heptanoic acid Drug Info [26]
2-(4-benzyl-piperidin-1-ylmethyl)-1H-indol-6-ol Drug Info [27]
2-(4-Phenoxy-benzyl)-1H-benzoimidazole Drug Info [28]
2-(4-Phenoxy-benzyl)-3H-benzoimidazol-4-ol Drug Info [28]
2-(4-Phenoxy-benzyl)-3H-benzoimidazol-5-ol Drug Info [28]
2-(4-Phenoxy-benzyl)-3H-benzoimidazol-5-ylamine Drug Info [28]
2-Methylamino-succinic acid(NMDA) Drug Info [29]
2-Pyridin-4-yl-1,2,3,4-tetrahydro-isoquinoline Drug Info [30]
3-Benzoyl-7-chloro-4-hydroxy-1H-quinolin-2-one Drug Info [31]
3-Hydroxy-1H-benzo[b]azepine-2,5-dione Drug Info [32]
3-Hydroxy-6-methyl-1H-benzo[b]azepine-2,5-dione Drug Info [32]
3-Hydroxy-7-nitro-1H-benzo[b]azepine-2,5-dione Drug Info [32]
3-Hydroxy-8-methyl-1H-benzo[b]azepine-2,5-dione Drug Info [32]
3-phenyl-4-hydroxyquinolin-2(1H)-one Drug Info [33]
4,5,7-Trichloro-3-hydroxy-1H-quinolin-2-one Drug Info [34]
4,6-Dichloro-1H-indole-2-carboxylic acid Drug Info [35]
4-(3,4-Dihydro-1H-isoquinolin-2-yl)-quinoline Drug Info [30]
4-Benzyl-1-(2-phenoxy-ethyl)-piperidine Drug Info [36]
4-Benzyl-1-phenethyl-piperidine hydrochloride Drug Info [37]
4-Bromo-3-hydroxy-1H-quinolin-2-one Drug Info [34]
4-Bromo-5,7-dichloro-3-hydroxy-1H-quinolin-2-one Drug Info [34]
4-Chloro-3-hydroxy-1H-quinolin-2-one Drug Info [34]
4-hydroxy-5-phenylthieno[2,3-b]pyridin-6(7H)-one Drug Info [33]
4-Phosphonomethyl-piperidine-2-carboxylic acid Drug Info [38]
4-[2-(3-Phenyl-propylamino)-ethyl]-phenol Drug Info [37]
4-[2-(4-Benzyl-piperidin-1-yl)-ethoxy]-phenol Drug Info [36]
4-[2-(4-Phenyl-butoxy)-ethyl]-phenol Drug Info [37]
4-[2-(4-Phenyl-butylamino)-ethyl]-phenol Drug Info [37]
4-[2-(4-Phenyl-piperidin-1-yl)-ethoxy]-phenol Drug Info [36]
4-[2-(5-Phenyl-pentylamino)-ethyl]-phenol Drug Info [37]
4-[2-(6-Phenyl-hexylamino)-ethyl]-phenol Drug Info [37]
4-[3-(4-Phenyl-butylamino)-propyl]-phenol Drug Info [39]
4-[3-(5-Phenyl-pentylamino)-propyl]-phenol Drug Info [37]
4-{2-[Ethyl-(4-phenyl-butyl)-amino]-ethyl}-phenol Drug Info [37]
5,7-Dichloro-3-hydroxy-1H-quinazoline-2,4-dione Drug Info [40]
5,7-Dichloro-4-hydroxy-3-phenyl-1H-quinolin-2-one Drug Info [31]
5,7-Dinitro-1,4-dihydro-quinoxaline-2,3-dione Drug Info [31]
6,7-Dichloro-3-hydroxy-1H-quinazoline-2,4-dione Drug Info [40]
6-Chloro-1,4-dihydro-quinoxaline-2,3-dione Drug Info [41]
6-Methoxy-2-(4-phenoxy-benzyl)-1H-benzoimidazole Drug Info [28]
6-Nitro-1,4-dihydro-quinoxaline-2,3-dione Drug Info [41]
6-Nitro-2-(4-phenoxy-benzyl)-1H-benzoimidazole Drug Info [28]
7-chloro-3-hydroxyquinazoline-2,4-dione Drug Info [42]
7-Chloro-3-nitro-3,4-dihydro-1H-quinolin-2-one Drug Info [31]
8-Bromo-3-hydroxy-1H-benzo[b]azepine-2,5-dione Drug Info [32]
8-Chloro-3-hydroxy-1H-benzo[b]azepine-2,5-dione Drug Info [32]
8-Ethyl-3-hydroxy-1H-benzo[b]azepine-2,5-dione Drug Info [32]
8-Fluoro-3-hydroxy-1H-benzo[b]azepine-2,5-dione Drug Info [32]
Ala-Pro-Glu Drug Info [25]
AP-7 Drug Info [43]
Benzyl 4-aminobutyl(3-aminopropyl)carbamate Drug Info [44]
Conantokin-G Drug Info [45]
Conantokin-R Drug Info [45]
DITOLYLGUANIDINE Drug Info [46]
DIZOCILPINE Drug Info [47]
DNQX Drug Info [48]
ELIPRODIL Drug Info [36]
GLUTAMATE Drug Info [43]
Gly-Amp-Glu Drug Info [25]
Gly-b7Pro-Glu Drug Info [25]
Gly-Hyp-Glu Drug Info [25]
Gly-Pip-Glu Drug Info [25]
H-Gly-D-dmP-Glu-OH Drug Info [49]
H-Gly-dmP-Glu-OH Drug Info [49]
H-Gly-PMe-Glu-OH Drug Info [49]
L-687414 Drug Info [31]
L-695902 Drug Info [31]
L-698532 Drug Info [33]
L-701324 Drug Info [33]
MDL-105519 Drug Info [50]
N,N'-Bis-(4-butoxy-phenyl)-guanidine Drug Info [46]
N,N'-Bis-(4-butyl-phenyl)-guanidine Drug Info [46]
N,N'-Bis-(4-ethyl-phenyl)-guanidine Drug Info [46]
N,N'-Bis-(4-hexyl-phenyl)-guanidine Drug Info [46]
N,N'-Bis-(4-isopropyl-phenyl)-guanidine Drug Info [46]
N,N'-Bis-(4-sec-butyl-phenyl)-guanidine Drug Info [46]
N-(2-methoxybenzyl)cinnamamidine Drug Info [51]
N-(3-phenethoxybenzyl)-4-hydroxybenzamide Drug Info [52]
N-(4-(benzyloxy)phenethyl)pyridin-4-amine Drug Info [53]
NBQX Drug Info [54]
Nle-Pro-Glu Drug Info [25]
Phe-Pro-Glu Drug Info [25]
PHENCYCLIDINE Drug Info [55]
Phenethyl-(3-phenyl-propyl)-amine Drug Info [37]
Phenethyl-(4-phenyl-butyl)-amine Drug Info [37]
RPR-104632 Drug Info [56]
RPR-118723 Drug Info [56]
TRANSTORINE Drug Info [35]
YM-90K Drug Info [57]
Antagonist Besonprodil Drug Info [58]
CERC-301 Drug Info [59]
Co 101244 Drug Info [60]
Conantokins G Drug Info [61]
Conantokins T Drug Info [61]
CP-101,606 Drug Info [62]
d-AP5 Drug Info [24]
d-CCPene Drug Info [24]
EVT-101 Drug Info [58]
EVT-103 Drug Info [63]
Ifenprodil Drug Info [64]
LY233053 Drug Info [24]
Neu-2000 Drug Info [65]
NMDA NR2B antagonists Drug Info [24]
NP93-31 Drug Info [24]
NVP-AAM077 Drug Info [66]
RGH-896 Drug Info [4]
Ro 63-1908 Drug Info [67]
RO-25-6981 Drug Info [68]
Tenocyclidine Drug Info [69]
UBP141 Drug Info [26]
[3H]CGP39653 Drug Info [24]
[3H]CGP61594 Drug Info [24]
[3H]CGS19755 Drug Info [24]
[3H]CPP Drug Info [24]
[3H]L689560 Drug Info [24]
[3H]MDL105519 Drug Info [24]
Modulator CN-2097 Drug Info [24]
Modulator (allosteric modulator) DQP-1105 Drug Info [70]
Blocker (channel blocker) N1-dansyl-spermine Drug Info [24]
[3H]dizocilpine Drug Info [24]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Ras signaling pathway
Rap1 signaling pathway
cAMP signaling pathway
Neuroactive ligand-receptor interaction
Circadian entrainment
Long-term potentiation
Glutamatergic synapse
Dopaminergic synapse
Alzheimer&#039
s disease
Amyotrophic lateral sclerosis (ALS)
Huntington&#039
Cocaine addiction
Amphetamine addiction
Nicotine addiction
Alcoholism
Systemic lupus erythematosus
PANTHER Pathway Huntington disease
Ionotropic glutamate receptor pathway
Metabotropic glutamate receptor group III pathway
Metabotropic glutamate receptor group I pathway
Muscarinic acetylcholine receptor 1 and 3 signaling pathway
Pathway Interaction Database ErbB4 signaling events
Reelin signaling pathway
Reactome EPHB-mediated forward signaling
Unblocking of NMDA receptor, glutamate binding and activation
CREB phosphorylation through the activation of CaMKII
Ras activation uopn Ca2+ infux through NMDA receptor
RAF/MAP kinase cascade
WikiPathways Hypothetical Network for Drug Addiction
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
BDNF signaling pathway
References
REF 1ClinicalTrials.gov (NCT02459236) A Study of Intermittent Doses of CERC-301 in MDD.
REF 2ClinicalTrials.gov (NCT00073476) A Study to Evaluate the Efficacy and Safety of CP-101,606 in Subjects With an Acute Stroke. U.S. National Institutes of Health.
REF 3ClinicalTrials.gov (NCT00001929) Treatment of Parkinson's Disease With Eliprodil. U.S. National Institutes of Health.
REF 4Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
REF 5(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: 4264).
REF 6Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025797)
REF 7Effects of the novel 5-hydroxytryptamine reuptake inhibitor indalpine and ethanol on psychomotor performance. Arzneimittelforschung. 1988 Jan;38(1):98-102.
REF 8(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: 5472).
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023880)
REF 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002155)
REF 11Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013599)
REF 12Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030864)
REF 13(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: 2403).
REF 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000713)
REF 15Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001829)
REF 16Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003055)
REF 17Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006620)
REF 18(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: 4240).
REF 19L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats. Psychopharmacology (Berl). 1999 Apr;143(3):235-43.
REF 20Anticonvulsant and behavioral profile of L-701,324, a potent, orally active antagonist at the glycine modulatory site on the N-methyl-D-aspartate receptor complex. J Pharmacol Exp Ther. 1996 Nov;279(2):492-501.
REF 21Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007135)
REF 22Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009657)
REF 23Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004459)
REF 24(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).
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REF 47J Med Chem. 1995 Jun 23;38(13):2483-9.Synthesis and evaluation of 6,11-ethanohexahydrobenzo[b]quinolizidines: a new class of noncompetitive N-methyl-D-aspartate antagonists.
REF 48J Med Chem. 1991 Apr;34(4):1243-52.Kynurenic acid derivatives. Structure-activity relationships for excitatory amino acid antagonism and identification of potent and selective antagonists at the glycine site on the N-methyl-D-aspartate receptor.
REF 49Bioorg Med Chem Lett. 2006 Jul 1;16(13):3396-400. Epub 2006 May 2.The neuroprotective activity of GPE tripeptide analogues does not correlate with glutamate receptor binding affinity.
REF 50J Med Chem. 2005 Feb 24;48(4):995-1018.CoMFA, synthesis, and pharmacological evaluation of (E)-3-(2-carboxy-2-arylvinyl)-4,6-dichloro-1H-indole-2-carboxylic acids: 3-[2-(3-aminophenyl)-2-carboxyvinyl]-4,6-dichloro-1H-indole-2-carboxylic acid, a potent selective glycine-site NMDA receptor antagonist.
REF 51Bioorg Med Chem Lett. 2005 Dec 15;15(24):5439-41. Epub 2005 Oct 5.Indole-2-carboxamidines as novel NR2B selective NMDA receptor antagonists.
REF 52Bioorg Med Chem Lett. 2007 Oct 15;17(20):5537-42. Epub 2007 Aug 19.Structure-activity relationship study of novel NR2B-selective antagonists with arylamides to avoid reactive metabolites formation.
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REF 55J Med Chem. 1996 Nov 22;39(24):4844-52.Synthesis and biological activity of conformationally restricted analogs of milnacipran: (1S,2R)-1-phenyl-2-[(S)-1-aminopropyl]-N,N-diethylcyclopropanecarboxamide, an efficient noncompetitive N-methyl-D-aspartic acid receptor antagonist.
REF 56J Med Chem. 2000 Jun 15;43(12):2371-81.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.
REF 57Bioorg Med Chem Lett. 2000 May 15;10(10):1133-7.4,10-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 in vivo activity.
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