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glycogen synthase kinase 3 alpha

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Target id: 2029

Nomenclature: glycogen synthase kinase 3 alpha

Abbreviated Name: GSK3A

Family: GSK subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 483 19q13.2 GSK3A glycogen synthase kinase 3 alpha
Mouse - 490 7 A3 Gsk3a glycogen synthase kinase 3 alpha
Rat - 483 1q21 Gsk3a glycogen synthase kinase 3 alpha
Previous and Unofficial Names Click here for help
GSK-3 alpha
Database Links Click here for help
Alphafold P49840 (Hs), Q2NL51 (Mm), P18265 (Rn)
BRENDA 2.7.11.26
ChEMBL Target CHEMBL2850 (Hs), CHEMBL2176843 (Mm), CHEMBL1075224 (Rn)
Ensembl Gene ENSG00000105723 (Hs), ENSMUSG00000057177 (Mm), ENSRNOG00000020417 (Rn)
Entrez Gene 2931 (Hs), 606496 (Mm), 50686 (Rn)
Human Protein Atlas ENSG00000105723 (Hs)
KEGG Enzyme 2.7.11.26
KEGG Gene hsa:2931 (Hs), mmu:606496 (Mm), rno:50686 (Rn)
OMIM 606784 (Hs)
Pharos P49840 (Hs)
RefSeq Nucleotide NM_019884 (Hs), NM_001031667 (Mm), NM_017344 (Rn)
RefSeq Protein NP_063937 (Hs), NP_001026837 (Mm), NP_059040 (Rn)
UniProtKB P49840 (Hs), Q2NL51 (Mm), P18265 (Rn)
Wikipedia GSK3A (Hs)
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
AZD1080 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.2 pKi 5
⤷ pKi 8.2 (Ki 6.9x10-9 M) [5]
CHIR-98014 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 9.2 pIC50 11
⤷ pIC50 9.2 (IC50 6.5x10-10 M) [11]
GSK-3 inhibitor IX Small molecule or natural product Click here for species-specific activity table Pig Inhibition 8.3 pIC50 7,10
⤷ pIC50 8.3 (IC50 5x10-9 M) [7,10]
Description: GSK3α/β complex from pig brain
SB 216763 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.1 pIC50 2
⤷ pIC50 8.1 (IC50 9x10-9 M) [2]
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 8.0 pIC50 11
⤷ pIC50 8.0 (IC50 9.8x10-9 M) [11]
GSK-3 inhibitor X Small molecule or natural product Click here for species-specific activity table Pig Inhibition 8.0 pIC50 10
⤷ pIC50 8.0 (IC50 1x10-8 M) [10]
Description: Measured using GSK3 as a complex of α and β isozymes, isolated from pig brain
voruciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 9
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [9]
SB-415286 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 7.4 pIC50 2
⤷ pIC50 7.4 (IC50 3.8x10-8 M) [2]
aloisine A Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pIC50 8
⤷ pIC50 6.3 (IC50 5x10-7 M) [8]
rucaparib metabolite M324 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.2 pIC50 6
⤷ pIC50 6.2 (IC50 5.79x10-7 M) [6]
View species-specific inhibitor tables
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: 3,12
Key to terms and symbols Click column headers to sort
Target used in screen: GSK3A
Ligand Sp. Type Action Value Parameter
AT-7519 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
BMS-387032 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.6 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
R547 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.6 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
alvocidib Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.9 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.6 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.6 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.6 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 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: 1,4
Key to terms and symbols Click column headers to sort
Target used in screen: GSK3α/GSK3a
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 0.8 1.0 0.0
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.0 1.0 2.0
PKR inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.0 4.0 1.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 2.2 15.0 3.0
JNK inhibitor V Small molecule or natural product Hs Inhibitor Inhibition 2.4 1.0 -1.0
GSK-3 inhibitor IX Small molecule or natural product Hs Inhibitor Inhibition 3.6 -1.0 -1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 1.0 -1.5
kenpaullone Small molecule or natural product Hs Inhibitor Inhibition 5.9 5.0 0.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 3.0 2.0
GSK-3 inhibitor X Small molecule or natural product Hs Inhibitor Inhibition 6.5 4.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling

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. 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]

3. 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]

4. 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]

5. 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]

6. Hu H, Serra C, Zhang W, Scrivo A, Fernández-Carasa I, Consiglio A, Aytes A, Pujana MA, Llebaria A, Antolin AA. (2024) Identification of differential biological activity and synergy between the PARP inhibitor rucaparib and its major metabolite. Cell Chem Biol, 31 (5): 973-988.e4. [PMID:38335967]

7. 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]

8. Mettey Y, Gompel M, Thomas V, Garnier M, Leost M, Ceballos-Picot I, Noble M, Endicott J, Vierfond JM, Meijer L. (2003) Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. J Med Chem, 46 (2): 222-36. [PMID:12519061]

9. 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]

10. 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]

11. 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]

12. 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]

How to cite this page

GSK subfamily: glycogen synthase kinase 3 alpha. Last modified on 12/02/2024. Accessed on 04/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2029.