Top ▲

glycogen synthase kinase 3 beta

Click here for help

Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2030

Nomenclature: glycogen synthase kinase 3 beta

Abbreviated Name: GSK3B

Family: GSK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 420 3q13.33 GSK3B glycogen synthase kinase 3 beta
Mouse - 420 16 B3 Gsk3b glycogen synthase kinase 3 beta
Rat - 420 11q21 Gsk3b glycogen synthase kinase 3 beta
Previous and Unofficial Names Click here for help
GSK3 | GSK-3 beta | tau phosphorylating kinase I [22]
Database Links Click here for help
Alphafold P49841 (Hs), Q9WV60 (Mm), P18266 (Rn)
BRENDA 2.7.11.26
ChEMBL Target CHEMBL262 (Hs), CHEMBL1075321 (Mm), CHEMBL3669 (Rn)
Ensembl Gene ENSG00000082701 (Hs), ENSMUSG00000022812 (Mm), ENSRNOG00000002833 (Rn)
Entrez Gene 2932 (Hs), 56637 (Mm), 84027 (Rn)
Human Protein Atlas ENSG00000082701 (Hs)
KEGG Enzyme 2.7.11.26
KEGG Gene hsa:2932 (Hs), mmu:56637 (Mm), rno:84027 (Rn)
OMIM 605004 (Hs)
Pharos P49841 (Hs)
RefSeq Nucleotide NM_001146156 (Hs), NM_019827 (Mm), NM_032080 (Rn)
RefSeq Protein NP_001139628 (Hs), NP_062801 (Mm), NP_114469 (Rn)
SynPHARM 80337 (in complex with alsterpaullone)
82212 (in complex with AZD2858)
81001 (in complex with CHIR-99021)
80420 (in complex with GSK-3beta inhibitor VIII)
80430 (in complex with indirubin-3'-monoxime)
UniProtKB P49841 (Hs), Q9WV60 (Mm), P18266 (Rn)
Wikipedia GSK3B (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  GSK-3 Beta complexed with Indirubin-3'-monoxime
PDB Id:  1Q41
Resolution:  2.1Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  STRUCTURE OF GLYCOGEN SYNTHASE KINASE-3 (GSK3B)
PDB Id:  1I09
Resolution:  2.7Å
Species:  Human
References:  43
Enzyme Reaction Click here for help
EC Number: 2.7.11.26

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AZD2858 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.3 pKi 4
⤷ pKi 8.3 (Ki 4.9x10-9 M) [4]
GSK-3 inhibitor XIII Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pKi 3
⤷ pKi 7.7 (Ki 2.2x10-8 M) [3]
GSK-3beta inhibitor XI Small molecule or natural product Primary target of this compound Oc Inhibition 7.6 pKi 32
⤷ pKi 7.6 (Ki 2.5x10-8 M) [32]
AZD1080 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.5 pKi 21
⤷ pKi 7.5 (Ki 3.1x10-8 M) [21]
GSK-3beta inhibitor VIII Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.4 pKi 8
⤷ pKi 7.4 (Ki 3.8x10-8 M) [8]
tideglusib Small molecule or natural product Hs Irreversible inhibition 7.3 pKi 14
⤷ pKi 7.3 (Ki 5x10-8 M) [14]
CHIR-98014 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.2 pIC50 37
⤷ pIC50 9.2 (IC50 5.8x10-10 M) [37]
alsterpaullone 2-cyanoethyl Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.1 pIC50 17
⤷ pIC50 9.1 (IC50 8x10-10 M) [17]
LY2090314 Small molecule or natural product Primary target of this compound Hs Inhibition 9.0 pIC50 16
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [16]
Description: Inhibition of GSK-3β-mediated phosphoryaltion of phosph0-CREB
GSK-3β inhibitor 3 [PMID: 25845281] Small molecule or natural product Ligand has a PDB structure Hs Inhibition 9.0 pIC50 41
⤷ pIC50 9.0 (IC50 1.1x10-9 M) [41]
Description: In vitro GSK-3β inhibitory activity
RGB-286638 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 9
⤷ pIC50 8.5 (IC50 3x10-9 M) [9]
alsterpaullone Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 27
⤷ pIC50 8.4 (IC50 4x10-9 M) [27]
GSK-3 inhibitor IX Small molecule or natural product Click here for species-specific activity table Pig Inhibition 8.3 pIC50 29,36
⤷ pIC50 8.3 (IC50 5x10-9 M) [29,36]
Description: GSK3α/β complex from pig brain
laduviglusib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pIC50 37
⤷ pIC50 8.2 (IC50 6.7x10-9 M) [37]
SB 216763 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition ~8.1 pIC50 11
⤷ pIC50 ~8.1 (IC50 ~9x10-9 M) [11]
GSK-3 inhibitor X Small molecule or natural product Click here for species-specific activity table Pig Inhibition 8.0 pIC50 36
⤷ pIC50 8.0 (IC50 1x10-8 M) [36]
Description: Measured using GSK3 as a complex of α and β isozymes, isolated from pig brain
GNF4877 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 40
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [40]
compound 2 [PMID: 22560567] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 10
⤷ pIC50 7.8 (IC50 1.72x10-8 M) [10]
1-azakenpaullone Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.7 pIC50 25
⤷ pIC50 7.7 (IC50 1.8x10-8 M) [25]
indirubin-3'-monoxime Small molecule or natural product Primary target of this compound Hs Inhibition 7.7 pIC50 26
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [26]
kenpaullone Small molecule or natural product Primary target of this compound Hs Inhibition 7.6 pIC50 26
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [26]
compound 52 [PMID: 9677190] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 17
⤷ pIC50 7.5 (IC50 3x10-8 M) [17]
TWS119 Small molecule or natural product Primary target of this compound Hs Inhibition 7.5 pIC50 13
⤷ pIC50 7.5 (IC50 3x10-8 M) [13]
SB-415286 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition ~7.4 pIC50 11
⤷ pIC50 ~7.4 (IC50 ~3.8x10-8 M) [11]
IM-12 Small molecule or natural product Primary target of this compound Hs Inhibition 7.3 pIC50 39
⤷ pIC50 7.3 (IC50 5.3x10-8 M) [39]
compound 2f [Jiang et al., 2018] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 24
⤷ pIC50 7.2 (IC50 6.6x10-8 M) [24]
voruciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pIC50 34
⤷ pIC50 7.2 (IC50 7.1x10-8 M) [34]
compound 89S [PMID: 19115845] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pIC50 30
⤷ pIC50 6.8 (IC50 1.46x10-7 M) [30]
compound 4g [PMID: 2680437] Small molecule or natural product Immunopharmacology Ligand Hs Inhibition 6.7 pIC50 42
⤷ pIC50 6.7 (IC50 1.9x10-7 M) [42]
Description: Evaluated in a Kinase-Glo assay.
compound 5 [PMID: 19338355] Small molecule or natural product Ligand has a PDB structure Hs Inhibition 6.6 pIC50 19
⤷ pIC50 6.6 (IC50 2.47x10-7 M) [19]
Description: In a cell-free assay.
compound 5b [PMID: 24900464] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.6 pIC50 15
⤷ pIC50 6.6 (IC50 2.5x10-7 M) [15]
GSK-3beta inhibitor II Small molecule or natural product Primary target of this compound Hs Inhibition 6.4 pIC50 31
⤷ pIC50 6.4 (IC50 3.9x10-7 M) [31]
isogranulatimide Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.3 pIC50 17,23
⤷ pIC50 6.3 (IC50 5x10-7 M) [17,23]
7-hydroxystaurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pIC50 23
⤷ pIC50 6.3 (IC50 5x10-7 M) [23]
BX-795 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.2 pIC50 18
⤷ pIC50 6.2 (IC50 6.2x10-7 M) [18]
elraglusib Small molecule or natural product Hs Inhibition 6.2 pIC50 19
⤷ pIC50 6.2 (IC50 7.1x10-7 M) [19]
Description: Measuring inhibition of GSK-3β-mediated phosphorylation of a peptide substrate in vitro.
Cdk/Crk inhibitor Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pIC50 17
⤷ pIC50 6.1 (IC50 7.54x10-7 M) [17]
Cdk1/5 inhibitor Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 pIC50 17
⤷ pIC50 6.0 (IC50 1x10-6 M) [17]
GSK-3beta inhibitor I Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 5.8 pIC50 46
⤷ pIC50 5.8 (IC50 1.4x10-6 M) [46]
GSK2646264 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.3 pIC50 2
⤷ pIC50 5.3 (IC50 5.012x10-6 M) [2]
compound 4-3 [PMID: 34027661] Small molecule or natural product Hs Inhibition 5.2 pIC50 47
⤷ pIC50 5.2 (IC50 6.6x10-6 M) [47]
BX-912 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.1 pIC50 18
⤷ pIC50 5.1 (IC50 7.4x10-6 M) [18]
Li+ Approved drug Click here for species-specific activity table Hs Inhibition 2.6 pIC50 38
⤷ pIC50 2.6 (IC50 2.5x10-3 M) Competive with Mg2+ [38]
View species-specific inhibitor tables
Inhibitor Comments
GSK3β may be the primary target of the approved drug lithium, which inhibits GSK3β activity by approximately 80% [44].
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 12,45
Key to terms and symbols Click column headers to sort
Target used in screen: GSK3B
Ligand Sp. Type Action Value Parameter
enzastaurin Small molecule or natural product Hs Inhibitor Inhibition 8.1 pKd
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
BMS-387032 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.9 pKd
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.5 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,20
Key to terms and symbols Click column headers to sort
Target used in screen: GSK3β/GSK3b
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.7 -1.0 3.0
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 2.7 -3.0 0.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 3.8 -1.0 0.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.4 7.5 4.5
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 4.6 40.0 23.0
JNK inhibitor V Small molecule or natural product Hs Inhibitor Inhibition 6.2 8.0 1.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 4.0 0.0
GF109203X Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 24.0 3.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 4.0 0.0
Ro-32-0432 Small molecule or natural product Hs Inhibitor Inhibition 11.2
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
GSK3β plays an essential function in T cell differentiation and proliferation, and its activity is inhibited following antigen-driven T cell activation [6-7,28,33]. Recent evidence shows that in CD4+ T cells, inactivation of GSK3β is mediated by the GTPase GIMAP5 (GIMAP5; Q96F15), and that GIMAP5 represents an important checkpoint in T cell proliferation [35]. Ablation of Gimap5 activity leads to constitutive GSK3β activation and substantially reduced CD4+ T cell proliferation in vitro and in in vivo rodent models. A loss-of-function mutation in GIMAP5 has been identified in a patient with lymphopenia (see rs72650695; p.Leu204Pro). Treatment of this patient's T cells, ex vivo, with lithium chloride (a GSK3 inhibitor) rescues their proliferative potential.
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Immuno Process:  Immune regulation
Immuno Process:  Immune system development

References

Show »

1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Barker MD, Liddle J, Atkinson FL, Wilson DM, Dickson MC, Ramirez-Molina C, Lewis H, Davis RP, Somers DO, Neu M et al.. (2018) Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. Bioorg Med Chem Lett, 28 (21): 3458-3462. [PMID:30249354]

3. Bebbington D, Binch H, Charrier JD, Everitt S, Fraysse D, Golec J, Kay D, Knegtel R, Mak C, Mazzei F et al.. (2009) The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorg Med Chem Lett, 19 (13): 3586-92. [PMID:19447622]

4. Berg S, Bergh M, Hellberg S, Högdin K, Lo-Alfredsson Y, Söderman P, von Berg S, Weigelt T, Ormö M, Xue Y et al.. (2012) Discovery of novel potent and highly selective glycogen synthase kinase-3β (GSK3β) inhibitors for Alzheimer's disease: design, synthesis, and characterization of pyrazines. J Med Chem, 55 (21): 9107-19. [PMID:22489897]

5. Bertrand JA, Thieffine S, Vulpetti A, Cristiani C, Valsasina B, Knapp S, Kalisz HM, Flocco M. (2003) Structural characterization of the GSK-3beta active site using selective and non-selective ATP-mimetic inhibitors. J Mol Biol, 333 (2): 393-407. [PMID:14529625]

6. Beurel E, Kaidanovich-Beilin O, Yeh WI, Song L, Palomo V, Michalek SM, Woodgett JR, Harrington LE, Eldar-Finkelman H, Martinez A et al.. (2013) Regulation of Th1 cells and experimental autoimmune encephalomyelitis by glycogen synthase kinase-3. J Immunol, 190 (10): 5000-11. [PMID:23606540]

7. Beurel E, Yeh WI, Michalek SM, Harrington LE, Jope RS. (2011) Glycogen synthase kinase-3 is an early determinant in the differentiation of pathogenic Th17 cells. J Immunol, 186 (3): 1391-8. [PMID:21191064]

8. Bhat R, Xue Y, Berg S, Hellberg S, Ormö M, Nilsson Y, Radesäter AC, Jerning E, Markgren PO, Borgegård T et al.. (2003) Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem, 278 (46): 45937-45. [PMID:12928438]

9. Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G et al.. (2013) Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia, 27 (12): 2366-75. [PMID:23807770]

10. Coffman K, Brodney M, Cook J, Lanyon L, Pandit J, Sakya S, Schachter J, Tseng-Lovering E, Wessel M. (2011) 6-amino-4-(pyrimidin-4-yl)pyridones: novel glycogen synthase kinase-3β inhibitors. Bioorg Med Chem Lett, 21 (5): 1429-33. [PMID:21295469]

11. Coghlan MP, Culbert AA, Cross DA, Corcoran SL, Yates JW, Pearce NJ, Rausch OL, Murphy GJ, Carter PS, Roxbee Cox L et al.. (2000) Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol, 7 (10): 793-803. [PMID:11033082]

12. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

13. Ding S, Wu TY, Brinker A, Peters EC, Hur W, Gray NS, Schultz PG. (2003) Synthetic small molecules that control stem cell fate. Proc Natl Acad Sci USA, 100 (13): 7632-7. [PMID:12794184]

14. Domínguez JM, Fuertes A, Orozco L, del Monte-Millán M, Delgado E, Medina M. (2012) Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem, 287 (2): 893-904. [PMID:22102280]

15. Dowling JE, Chuaqui C, Pontz TW, Lyne PD, Larsen NA, Block MH, Chen H, Su N, Wu A, Russell D et al.. (2012) Potent and Selective Inhibitors of CK2 Kinase Identified through Structure-Guided Hybridization. ACS Med Chem Lett, 3 (4): 278-83. [PMID:24900464]

16. Engler TA, Henry JR, Malhotra S, Cunningham B, Furness K, Brozinick J, Burkholder TP, Clay MP, Clayton J, Diefenbacher C et al.. (2004) Substituted 3-imidazo[1,2-a]pyridin-3-yl- 4-(1,2,3,4-tetrahydro-[1,4]diazepino-[6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3. J Med Chem, 47 (16): 3934-7. [PMID:15267232]

17. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S. (2007) A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci USA, 104 (51): 20523-8. [PMID:18077363]

18. Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S et al.. (2005) Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. J Biol Chem, 280 (20): 19867-74. [PMID:15772071]

19. Gaisina IN, Gallier F, Ougolkov AV, Kim KH, Kurome T, Guo S, Holzle D, Luchini DN, Blond SY, Billadeau DD et al.. (2009) 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, 52 (7): 1853-63. [PMID:19338355]

20. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

21. Georgievska B, Sandin J, Doherty J, Mörtberg A, Neelissen J, Andersson A, Gruber S, Nilsson Y, Schött P, Arvidsson PI et al.. (2013) AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans. J Neurochem, 125 (3): 446-56. [PMID:23410232]

22. Ishiguro K, Shiratsuchi A, Sato S, Omori A, Arioka M, Kobayashi S, Uchida T, Imahori K. (1993) Glycogen synthase kinase 3 beta is identical to tau protein kinase I generating several epitopes of paired helical filaments. FEBS Lett, 325 (3): 167-72. [PMID:7686508]

23. Jiang X, Zhao B, Britton R, Lim LY, Leong D, Sanghera JS, Zhou BB, Piers E, Andersen RJ, Roberge M. (2004) Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide. Mol Cancer Ther, 3 (10): 1221-7. [PMID:15486189]

24. Jiang XY, Chen TK, Zhou JT, He SY, Yang HY, Chen Y, Qu W, Feng F, Sun HP. (2018) Dual GSK-3β/AChE Inhibitors as a New Strategy for Multitargeting Anti-Alzheimer's Disease Drug Discovery. ACS Med Chem Lett, 9 (3): 171-176. [PMID:29541355]

25. Kunick C, Lauenroth K, Leost M, Meijer L, Lemcke T. (2004) 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett, 14 (2): 413-6. [PMID:14698171]

26. Leclerc S, Garnier M, Hoessel R, Marko D, Bibb JA, Snyder GL, Greengard P, Biernat J, Wu YZ, Mandelkow EM et al.. (2001) Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors?. J Biol Chem, 276 (1): 251-60. [PMID:11013232]

27. Leost M, Schultz C, Link A, Wu YZ, Biernat J, Mandelkow EM, Bibb JA, Snyder GL, Greengard P, Zaharevitz DW et al.. (2000) Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/p25. Eur J Biochem, 267 (19): 5983-94. [PMID:10998059]

28. Lovatt M, Bijlmakers MJ. (2010) Stabilisation of β-catenin downstream of T cell receptor signalling. PLoS ONE, 5 (9). [PMID:20862283]

29. Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R et al.. (2003) GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol, 10 (12): 1255-66. [PMID:14700633]

30. Menichincheri M, Bargiotti A, Berthelsen J, Bertrand JA, Bossi R, Ciavolella A, Cirla A, Cristiani C, Croci V, D'Alessio R et al.. (2009) First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. J Med Chem, 52 (2): 293-307. [PMID:19115845]

31. Naerum L, Nørskov-Lauritsen L, Olesen PH. (2002) Scaffold hopping and optimization towards libraries of glycogen synthase kinase-3 inhibitors. Bioorg Med Chem Lett, 12 (11): 1525-8. [PMID:12031334]

32. O'Neill DJ, Shen L, Prouty C, Conway BR, Westover L, Xu JZ, Zhang HC, Maryanoff BE, Murray WV, Demarest KT et al.. (2004) Design, synthesis, and biological evaluation of novel 7-azaindolyl-heteroaryl-maleimides as potent and selective glycogen synthase kinase-3beta (GSK-3beta) inhibitors. Bioorg Med Chem, 12 (12): 3167-85. [PMID:15158785]

33. Ohteki T, Parsons M, Zakarian A, Jones RG, Nguyen LT, Woodgett JR, Ohashi PS. (2000) Negative regulation of T cell proliferation and interleukin 2 production by the serine threonine kinase GSK-3. J Exp Med, 192 (1): 99-104. [PMID:10880530]

34. Paiva C, Godbersen JC, Soderquist RS, Rowland T, Kilmarx S, Spurgeon SE, Brown JR, Srinivasa SP, Danilov AV. (2015) Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. PLoS ONE, 10 (11): e0143685. [PMID:26606677]

35. Patterson AR, Endale M, Lampe K, Aksoylar HI, Flagg A, Woodgett JR, Hildeman D, Jordan MB, Singh H, Kucuk Z et al.. (2018) Gimap5-dependent inactivation of GSK3β is required for CD4+ T cell homeostasis and prevention of immune pathology. Nat Commun, 9 (1): 430. [PMID:29382851]

36. Polychronopoulos P, Magiatis P, Skaltsounis AL, Myrianthopoulos V, Mikros E, Tarricone A, Musacchio A, Roe SM, Pearl L, Leost M et al.. (2004) Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem, 47 (4): 935-46. [PMID:14761195]

37. Ring DB, Johnson KW, Henriksen EJ, Nuss JM, Goff D, Kinnick TR, Ma ST, Reeder JW, Samuels I, Slabiak T et al.. (2003) Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes, 52 (3): 588-95. [PMID:12606497]

38. Ryves WJ, Harwood AJ. (2001) Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem Biophys Res Commun, 280 (3): 720-5. [PMID:11162580]

39. Schmöle AC, Brennführer A, Karapetyan G, Jaster R, Pews-Davtyan A, Hübner R, Ortinau S, Beller M, Rolfs A, Frech MJ. (2010) Novel indolylmaleimide acts as GSK-3beta inhibitor in human neural progenitor cells. Bioorg Med Chem, 18 (18): 6785-95. [PMID:20708937]

40. Shen W, Taylor B, Jin Q, Nguyen-Tran V, Meeusen S, Zhang YQ, Kamireddy A, Swafford A, Powers AF, Walker J et al.. (2015) Inhibition of DYRK1A and GSK3B induces human β-cell proliferation. Nat Commun, 6: 8372. [PMID:26496802]

41. Sivaprakasam P, Han X, Civiello RL, Jacutin-Porte S, Kish K, Pokross M, Lewis HA, Ahmed N, Szapiel N, Newitt JA et al.. (2015) Discovery of new acylaminopyridines as GSK-3 inhibitors by a structure guided in-depth exploration of chemical space around a pyrrolopyridinone core. Bioorg Med Chem Lett, 25 (9): 1856-63. [PMID:25845281]

42. Tantray MA, Khan I, Hamid H, Alam MS, Umar S, Ali Y, Sharma K, Hussain F. (2016) Synthesis of Novel Oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles as Glycogen Synthase Kinase-3β Inhibitors with Anti-inflammatory Potential. Chem Biol Drug Des, 87 (6): 918-26. [PMID:26804375]

43. ter Haar E, Coll JT, Austen DA, Hsiao HM, Swenson L, Jain J. (2001) Structure of GSK3beta reveals a primed phosphorylation mechanism. Nat Struct Biol, 8 (7): 593-6. [PMID:11427888]

44. Werstuck GH, Kim AJ, Brenstrum T, Ohnmacht SA, Panna E, Capretta A. (2004) Examining the correlations between GSK-3 inhibitory properties and anti-convulsant efficacy of valproate and valproate-related compounds. Bioorg Med Chem Lett, 14 (22): 5465-7. [PMID:15482904]

45. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

46. Zhang P, Hu HR, Huang ZH, Lei JY, Chu Y, Ye DY. (2012) Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3β inhibitors through virtual screening. Bioorg Med Chem Lett, 22 (23): 7232-6. [PMID:23099099]

47. Zhang P, Min Z, Gao Y, Bian J, Lin X, He J, Ye D, Li Y, Peng C, Cheng Y et al.. (2021) Discovery of Novel Benzothiazepinones as Irreversible Covalent Glycogen Synthase Kinase 3β Inhibitors for the Treatment of Acute Promyelocytic Leukemia. J Med Chem, 64 (11): 7341-7358. [PMID:34027661]

How to cite this page

GSK subfamily: glycogen synthase kinase 3 beta. Last modified on 26/05/2021. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2030.