General Information of Drug Therapeutic Target (DTT) (ID: TT9PB26)

DTT Name Presynaptic density protein 95 (DLG4)
Synonyms Synapse-associated protein 90; SAP90; SAP-90; Postsynaptic density-95; Postsynaptic density protein 95; PSD95; PSD-95; Disks large homolog 4; Discs, large homolog 4
Gene Name DLG4
DTT Type
Clinical trial target
[1]
BioChemical Class
Ezrin/radixin/moesin-binding phosphoprotein 50
UniProt ID
DLG4_HUMAN
TTD ID
T04507
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDCLCIVTTKKYRYQDEDTPPLEHSPAHLPNQANSPPVIVNTDTLEAPGYELQVNGTEGE
MEYEEITLERGNSGLGFSIAGGTDNPHIGDDPSIFITKIIPGGAAAQDGRLRVNDSILFV
NEVDVREVTHSAAVEALKEAGSIVRLYVMRRKPPAEKVMEIKLIKGPKGLGFSIAGGVGN
QHIPGDNSIYVTKIIEGGAAHKDGRLQIGDKILAVNSVGLEDVMHEDAVAALKNTYDVVY
LKVAKPSNAYLSDSYAPPDITTSYSQHLDNEISHSSYLGTDYPTAMTPTSPRRYSPVAKD
LLGEEDIPREPRRIVIHRGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGELRKGDQIL
SVNGVDLRNASHEQAAIALKNAGQTVTIIAQYKPEEYSRFEAKIHDLREQLMNSSLGSGT
ASLRSNPKRGFYIRALFDYDKTKDCGFLSQALSFRFGDVLHVIDASDEEWWQARRVHSDS
ETDDIGFIPSKRRVERREWSRLKAKDWGSSSGSQGREDSVLSYETVTQMEVHYARPIIIL
GPTKDRANDDLLSEFPDKFGSCVPHTTRPKREYEIDGRDYHFVSSREKMEKDIQAHKFIE
AGQYNSHLYGTSVQSVREVAEQGKHCILDVSANAVRRLQAAHLHPIAIFIRPRSLENVLE
INKRITEEQARKAFDRATKLEQEFTECFSAIVEGDSFEEIYHKVKRVIEDLSGPYIWVPA
RERL
Function
Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels.
KEGG Pathway
Hippo signaling pathway (hsa04390 )
Glutamatergic synapse (hsa04724 )
Huntington's disease (hsa05016 )
Cocaine addiction (hsa05030 )
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 )
RHO GTPases activate CIT (R-HSA-5625900 )
RAF/MAP kinase cascade (R-HSA-5673001 )
Trafficking of AMPA receptors (R-HSA-399719 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Tat-NR2B9c DMD6AUX Cerebrovascular ischaemia 8B1Z Phase 3 [1]
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18 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
2-Methyl-2,4-Pentanediol DMD45CU Discovery agent N.A. Investigative [2]
FETAV DMO1N2T Discovery agent N.A. Investigative [3]
Guanosine-5'-Monophosphate DM3SLZK Discovery agent N.A. Investigative [2]
KSG-LDTKNYKQTSV DM5DTMQ Discovery agent N.A. Investigative [3]
KSG-YEKLSSIESDV DMPLFRC Discovery agent N.A. Investigative [3]
N-(3,4-Dichlorophenyl)propyl-ETAV DMTERF6 Discovery agent N.A. Investigative [3]
N-(3,4-Difluorophenyl)propyl-ETAV DMF2D4O Discovery agent N.A. Investigative [3]
N-(Naphthalene-2-yl)ethyl-ETAV DMG8KXR Discovery agent N.A. Investigative [3]
N-Benzyl-ETAV DMNPS4R Discovery agent N.A. Investigative [3]
N-Butyl-ETAV DMY3HEF Discovery agent N.A. Investigative [3]
N-Cyclohexylethyl-ETAV DMCH5M1 Discovery agent N.A. Investigative [3]
N-Cyclohexylmethyl-ETAV DMIC8Z6 Discovery agent N.A. Investigative [3]
N-Ethyl-ETAV DMPTNI8 Discovery agent N.A. Investigative [3]
N-Methyl-ETAV DMP1EF6 Discovery agent N.A. Investigative [3]
N-Phenylethyl-ETAV DM1VSO9 Discovery agent N.A. Investigative [3]
N-Phenylpropyl-ETAV DM90GNC Discovery agent N.A. Investigative [3]
N-Propyl-ETAV DMUTDNV Discovery agent N.A. Investigative [3]
YGRKKRRQRRR-KLSSIESDV DMV89B4 Discovery agent N.A. Investigative [3]
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⏷ Show the Full List of 18 Investigative Drug(s)

References

1 Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature. 2012 Feb 29;483(7388):213-7.
2 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
3 Modified peptides as potent inhibitors of the postsynaptic density-95/N-methyl-D-aspartate receptor interaction. J Med Chem. 2008 Oct 23;51(20):6450-9.