glycogen synthase kinase 3 alpha | GSK subfamily | IUPHAR/BPS Guide to PHARMACOLOGY

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glycogen synthase kinase 3 alpha

Target not currently curated in GtoImmuPdb

Target id: 2029

Nomenclature: glycogen synthase kinase 3 alpha

Abbreviated Name: GSK3A

Family: GSK subfamily

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 483 19q13 GSK3A glycogen synthase kinase 3 alpha
Mouse - 490 7 A3 Gsk3a glycogen synthase kinase 3 alpha
Rat - 483 1 q21 Gsk3a glycogen synthase kinase 3 alpha
Previous and Unofficial Names
GSK-3 alpha
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 2.7.11.26

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
voruciclib Hs Inhibition 7.8 pIC50 8
pIC50 7.8 (IC50 1.7x10-8 M) [8]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AZD1080 Hs Inhibition 8.2 pKi 5
pKi 8.2 (Ki 6.9x10-9 M) [5]
CHIR-98014 Hs Inhibition 9.2 pIC50 10
pIC50 9.2 (IC50 6.5x10-10 M) [10]
GSK-3 inhibitor IX Pig Inhibition 8.3 pIC50 6,9
pIC50 8.3 (IC50 5x10-9 M) [6,9]
Description: GSK3α/β complex from pig brain
SB 216763 Hs Inhibition 8.1 pIC50 2
pIC50 8.1 (IC50 9x10-9 M) [2]
CHIR-99021 Hs Inhibition 8.0 pIC50 10
pIC50 8.0 (IC50 9.8x10-9 M) [10]
GSK-3 inhibitor X Pig Inhibition 8.0 pIC50 9
pIC50 8.0 (IC50 1x10-8 M) [9]
Description: Measured using GSK3 as a complex of α and β isozymes, isolated from pig brain
SB-415286 Hs Inhibition 7.4 pIC50 2
pIC50 7.4 (IC50 3.8x10-8 M) [2]
aloisine A Hs Inhibition 6.3 pIC50 7
pIC50 6.3 (IC50 5x10-7 M) [7]
View species-specific inhibitor tables
DiscoveRx KINOMEscan® screen
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: 3,11

Key to terms and symbols Click column headers to sort
Target used in screen: GSK3A
Ligand Sp. Type Action Value Parameter
AT-7519 Hs Inhibitor Inhibition 7.6 pKd
BMS-387032 Hs Inhibitor Inhibition 7.6 pKd
staurosporine Hs Inhibitor Inhibition 6.8 pKd
R547 Hs Inhibitor Inhibition 6.6 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.4 pKd
alvocidib Hs Inhibitor Inhibition 5.9 pKd
lestaurtinib Hs Inhibitor Inhibition 5.6 pKd
tamatinib Hs Inhibitor Inhibition 5.6 pKd
midostaurin Hs Inhibitor Inhibition 5.6 pKd
SB203580 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
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 Hs Inhibitor Inhibition 0.8 1.0 0.0
alsterpaullone Hs Inhibitor Inhibition 1.0 1.0 2.0
PKR inhibitor Hs Inhibitor Inhibition 2.0 4.0 1.0
SB 218078 Hs Inhibitor Inhibition 2.2 15.0 3.0
JNK inhibitor V Hs Inhibitor Inhibition 2.4 1.0 -1.0
GSK-3 inhibitor IX Hs Inhibitor Inhibition 3.6 -1.0 -1.0
staurosporine Hs Inhibitor Inhibition 5.8 1.0 -1.5
kenpaullone Hs Inhibitor Inhibition 5.9 5.0 0.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 6.3 3.0 2.0
GSK-3 inhibitor X Hs Inhibitor Inhibition 6.5 4.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »

References

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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. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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 25/04/2018. Accessed on 15/09/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2029.