General Information of Drug Therapeutic Target (DTT) (ID: TTRZQE3)

DTT Name Glycogen synthase kinase-3 alpha (GSK-3A)
Synonyms Serine/threonineprotein kinase GSK3A; Serine/threonine-protein kinase GSK3A; Glycogen synthase kinase3 alpha; Glycogen synthase kinase 3; GSK3 alpha; GSK-3 alpha; GSK-3
Gene Name GSK3A
DTT Type
Successful target
[1]
BioChemical Class
Kinase
UniProt ID
GSK3A_HUMAN
TTD ID
T76910
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.11.26
Sequence
MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGV
GASSSGGGPGGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATLGQGPERSQEVAYT
DIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFY
SSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLTIPILYVKVYMYQLFRSLAYIHSQGV
CHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSS
IDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIK
AHPWTKVFKSRTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRCLGTQLPNNRPLP
PLFNFSAGELSIQPSLNAILIPPHLRSPAGTTTLTPSSQALTETPTSSDWQSTDATPTLT
NSS
Function
Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer. Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1.
KEGG Pathway
Chemokine signaling pathway (hsa04062 )
Dopaminergic synapse (hsa04728 )
Non-alcoholic fatty liver disease (hsa04932 )
Shigellosis (hsa05131 )
Reactome Pathway
XBP1(S) activates chaperone genes (R-HSA-381038 )
Constitutive Signaling by AKT1 E17K in Cancer (R-HSA-5674400 )
AKT phosphorylates targets in the cytosol (R-HSA-198323 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [1]
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2 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Lithium DMZ3OU6 Bipolar disorder 6A60 Phase 2 [2]
LY2090314 DMTBFE4 Acute myeloid leukaemia 2A60 Phase 2 [3]
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29 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AR-A014418 DMUPN01 Ovarian cancer 2C73 Patented [3]
CHIR-99021 DMB8MNU Allergic inflammation 4A80-4A85 Patented [3]
Indazole derivative 6 DMGO1CB N. A. N. A. Patented [3]
Indirubin derivative 2 DMLX183 N. A. N. A. Patented [3]
KENPAULLONE DMAGVXW Discovery agent N.A. Patented [3]
Maleimides derivative 1 DMINM8F N. A. N. A. Patented [3]
Maleimides derivative 2 DMUVYWE N. A. N. A. Patented [3]
Maleimides derivative 3 DMEFQND N. A. N. A. Patented [3]
N-naphtyl-N-benzylurea derivative 1 DMCVBPF N. A. N. A. Patented [3]
PMID27828716-Compound-15 DM3G21F N. A. N. A. Patented [3]
PMID27828716-Compound-16 DM9VXY7 N. A. N. A. Patented [3]
PMID27828716-Compound-17 DMR7V9E N. A. N. A. Patented [3]
PMID27828716-Compound-18 DMNR6KL N. A. N. A. Patented [3]
PMID27828716-Compound-19 DM8V7QH N. A. N. A. Patented [3]
PMID27828716-Compound-20 DMDA3PN N. A. N. A. Patented [3]
PMID27828716-Compound-21 DMO1NAR N. A. N. A. Patented [3]
PMID27828716-Compound-BIO-acetoxime DMUM5L6 Malignant glioma 2A00.0 Patented [3]
Pyrazole and benzimidazole derivative 1 DM05S2X N. A. N. A. Patented [3]
Pyrazolodihydropyridine derivative 1 DMKYX7J N. A. N. A. Patented [3]
Quinoline derivative 14 DMSRB8M N. A. N. A. Patented [3]
Quinoline derivative 15 DM7HD0T N. A. N. A. Patented [3]
Quinolinyl pyrazinyl urea derivative 1 DMCIKR3 N. A. N. A. Patented [3]
Quinolinyl pyrazinyl urea derivative 2 DMKJN9G N. A. N. A. Patented [3]
Spiroquinolone derivative 1 DMYJL2Z N. A. N. A. Patented [3]
TDZD-8 DMG6Q45 Malignant glioma 2A00.0 Patented [3]
Thiadiazolidindione derivative 1 DM1L3ZA N. A. N. A. Patented [3]
Thiadiazolidindione derivative 2 DM5AUL0 N. A. N. A. Patented [3]
Thiadiazolidindione derivative 3 DMNTZ93 N. A. N. A. Patented [3]
Tricyclic 5-quinolone derivative 1 DMYEDJI N. A. N. A. Patented [3]
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⏷ Show the Full List of 29 Patented Agent(s)
5 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
6-bromoindirubin-3-oxime DM12WYV Discovery agent N.A. Investigative [4]
AR-534 DMNJ632 Discovery agent N.A. Investigative [5]
Benzofuran-3-yl-(indol-3-yl)maleimides DMNVG1M Discovery agent N.A. Investigative [6]
Lithium chloride DMHYLQ2 Discovery agent N.A. Investigative [7]
SB216763 DMIYFQ5 Discovery agent N.A. Investigative [8]
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Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Sarcoma 2C82 Muscle tissue 4.67E-06 0.02 0.06
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References

1 Challenges and new opportunities in the investigation of new drug therapies to treat frontotemporal dementia. Expert Opin Ther Targets. 2008 Nov;12(11):1367-76.
2 The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874.
3 Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
4 Stable generation of serum- and feeder-free embryonic stem cell-derived mice with full germline-competency by using a GSK3 specific inhibitor. Genesis. 2009 Jun;47(6):414-22.
5 A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J Clin Invest. 2009 May;119(5):1382-95.
6 From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells. J Med Chem. 2009 Apr 9;52(7):1853-63.
7 Glycogen synthase kinase 3 beta (GSK-3 beta) as a therapeutic target in neuroAIDS. J Neuroimmune Pharmacol. 2007 Mar;2(1):93-6.
8 Intracellular protein phosphorylation in eosinophils and the functional relevance in cytokine production. Int Arch Allergy Immunol. 2009;149 Suppl 1:45-50.