GSK subfamily | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY

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Enzymes
Kinases (EC 2.7.x.x)
CMGC: Containing CDK, MAPK, GSK3, CLK families
Glycogen synthase kinase (GSK) family
GSK subfamily

GSK subfamily C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Enzymes

GSK3A (glycogen synthase kinase 3 alpha) Show summary »« Hide summary More detailed page

GSK3B (glycogen synthase kinase 3 beta) C Show summary »« Hide summary More detailed page

Target Id

2030

Nomenclature

glycogen synthase kinase 3 beta

Common abbreviation

GSK3B

Previous and unofficial names

GSK3 | GSK-3 beta | tau phosphorylating kinase I [4]

Genes

GSK3B (Hs), Gsk3b (Mm), Gsk3b (Rn)

Ensembl ID

ENSG00000082701 (Hs), ENSMUSG00000022812 (Mm), ENSRNOG00000002833 (Rn)

UniProtKB AC

P49841 (Hs), Q9WV60 (Mm), P18266 (Rn)

EC number

2.7.11.26

Inhibitors

CHIR-98014 pIC₅₀ 9.2 [7]

LY2090314 pIC₅₀ 9.0 [3]

CHIR-99021 pIC₅₀ 8.2 [7]

SB 216763 pIC₅₀ ~8.1 [2]

1-azakenpaullone pIC₅₀ 7.7 [5]

SB-415286 pIC₅₀ ~7.4 [2]

IM-12 pIC₅₀ 7.3 [8]

Selective inhibitors

AZD2858 pK_i 8.3 [1]

Comment

Due to its Tau phosphorylating activity, small molecule inhibitors of GSK-3β are being investigated as potential treatments for Alzheimer's disease (AD) [1]. GSK-3β also plays a role in canonical Wnt pathway signalling, the normal activity of which is crucial for the maintenance of normal bone mass. It is hypothesised that small molecule inhibitors of GSK-3β may provide effective therapeutics for the treatment of diseases characterised by low bone mass [6].

References

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1. 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]

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. 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]

4. 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]

5. 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]

6. Marsell R, Sisask G, Nilsson Y, Sundgren-Andersson AK, Andersson U, Larsson S, Nilsson O, Ljunggren O, Jonsson KB. (2012) GSK-3 inhibition by an orally active small molecule increases bone mass in rats. Bone, 50 (3): 619-27. [PMID:22142634]

7. 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]

8. 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]

How to cite this family page

Database page citation:

GSK subfamily. Accessed on 21/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=509.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Marrion NV, Peters JA, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2017) The Concise Guide to PHARMACOLOGY 2017/18: Enzymes. Br J Pharmacol. 174 Suppl 1: S272-S359.

GSK subfamily C

Enzymes

Further reading

References

How to cite this family page