GSK3 inhibitors: Development and therapeutic potential

Nature Reviews Drug Discovery

Volumn 3, Issue 6, 2004, Pages 479-487

  Cohen, Philip ^a   Goedert, Michel ^b  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

^b MRC LABORATORY OF MOLECULAR BIOLOGY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 (2,4 DICHLOROPHENYL) 3 (1 METHYL 3 INDOLYL)MALEIMIDE; 2 (3 CHLORO 4 HYDROXYANILINO) 3 (2 NITROPHENYL)MALEIMIDE; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; AR A 014418; AZAKENPAULLONE; BIS 7 INDOLYLMALEIMIDE; CHIR 98014; CHIR 98023; CHIR 99021; CYCLIC AMP DEPENDENT PROTEIN KINASE; CYCLIN DEPENDENT KINASE 1; CYCLIN DEPENDENT KINASE 5; CYCLIN DEPENDENT KINASE INHIBITOR; GLYCOGEN SYNTHASE KINASE 3; HUNTINGTIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INDIRUBIN; INSULIN; KENPAULLONE; LITHIUM CHLORIDE; MALEIMIDE DERIVATIVE; METFORMIN; PAULLONE DERIVATIVE; PROTEIN KINASE B; PROTEIN KINASE INHIBITOR; ROSCOVITINE; ROSIGLITAZONE; TAU PROTEIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALZHEIMER DISEASE; CELL FUNCTION; DEGENERATIVE DISEASE; DIABETES MELLITUS; DRUG DESIGN; DRUG POTENCY; DRUG POTENTIATION; DRUG STRUCTURE; DRUG TARGETING; ENTEROPATHY; ENZYME REGULATION; GLYCOGEN METABOLISM; HUMAN; HUNTINGTON CHOREA; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; STOMACH DISEASE; STRUCTURE ANALYSIS; TAUOPATHY;

EID: 3042635178     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrd1415     Document Type: Review

References (87)

1. Cohen, P. The fifteenth Colworth Medal Lecture. The hormonal control of glycogen metabolism in mammalian muscle by multivalent phosphorylation. Biochem. Soc. Trans. 7, 459-480 (1979).
2. Embi, N., Rylatt, D. B. & Cohen, P. Glycogen synthase kinase-3 from rabbit skeletal muscle; separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur. J. Biochem. 107, 519-527 (1980).
3. Fiol, C. J., Mahrenholz, A. M., Wang, Y., Roeske, R. W. & Roach, P. J. Formation of protein kinase recognition sites by covalent modification of the substrate; molecular mechanism for the synergistic action of casein kinase II and glycogen synthase kinase-3. J. Biol. Chem. 262, 14042-14048 (1987).
4. Sakanaka, C. Phosphorylation and regulation of β-catenin by casein kinase I. J. Biochem (Tokyo) 132, 687-703 (2002).
5. Gregory, M. A., Qi, Y. & Hann, S. R. Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localisation. J. Biol. Chem. 278, 51606-51612 (2003).
6. Frame, S. & Cohen, P. GSK3 takes centre stage more than 20 years after its discovery. Biochem. J. 359, 1-16 (2001).
7. Hughes, K., Mikolakaki, E., Pyte, S. E., Totty, N. F. & Woodgett, J. R. Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. EMBO J. 12, 803-808 (1993).
8. Cole, A., Frame, S. & Cohen, P. Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3 (GSK3) in mammalian cells is an autophosphorylation event. Biochem. J. 377, 249-255 (2004).
9. Cohen, P. The Croonian Lecture 1998. Identification of a protein kinase cascade of major importance in insulin signal transduction. Phil. Trans. R. Soc. Lond. B 354, 485-495 (1999).
10. Cohen, P. & Frame, S. The renaissance of GSK3. Nature Rev. Mol. Cell. Biol. 2, 769-776 (2001).
11. Frame, S., Cohen, P. & Biondi, R. M. A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation. Mol. Cell 7, 1321-1327.
12. Dajani, R. et al. Crystal structure of glycogen synthase kinase-3β: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 105, 721-732 (2001).
13. Kim, L. & Kimmel, A. R. GSK3, a master switch regulating cell fate specification and tumorigenesis. Curr. Opin. Genet. Dev 10, 508-514 (2000).
14. Seidensticker, M. J. & Behrens, J. Biochemical interactions in the Wnt pathway. Biochim. Biophys. Acta 1495, 168-182 (2000).
15. Eldar-Finkelman, H., Schreyer, S. A., Shinohara, M. M., LeBoeuf, R C. & Krebs, E. G. Increased glycogen synthase kinase-3 activity in diabetes- and obesity-prone C57BL/6J mice. Diabetes 48, 1-5 (1999).
16. Nikoulina, S. E. et al. Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes. Diabetes 49, 263-271 (2000).
17. Eldar-Finkelman, H. & Krebs, E. G. Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action. Proc. Natl. Acad. Sci. USA 94, 9660-9664 (1997).
18. Klein, P. S. & Melton, D. A. A molecular mechanism for the effect of lithium on development. Proc. Natl. Acad. Sci. USA 93, 8455-8459 (1996).
19. Stambolic, V., Ruel, L. & Woodgett, J. R. Lithium inhibits glycogen synthase Kinase-3 activity and mimics wingless signalling in intact cells. Curr. Biol. 6, 1664-1668 (1996).
20. Davies, S. P., Reddy, H., Caivano, M. & Cohen, P. Specificity and mechanism of acton of some commonly used protein kinase inhibitors. Biochem. J. 351, 95-105 (2000).
21. Cheng, K., Creacy, S. & Larner, J. 'Insulin-like' effects of lithium on isolated rat adipocytes. II. Specific activation of glycogen synthase. Mol. Cell. Biochem. 56, 183-189 (1983).
22. Coghlan, M. P. et al. Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem. Biol. 7, 793-803 (2000).
23. Norman, P. Emerging fundamental themes in modern medicinal chemistry. Drug News Persp. 14, 242-247 (2001).
24. Lochhead, P. A., Coghlan, M., Rice, S. Q. J. & Sutherland, C. Inhibition of GSK-3 selectively reduces glucose-6-phosphatase and phosphoenolpyruvate carboxykinase gene expression. Diabetes 50, 937-946 (2001).
25. LeClerc, C. et al. Indirubins inhibit glycogen synthase kinase-3β 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, 251-260 (2001).
26. Meijer, L. et al. GSK3-selective inhibitors derived from tyrian purple indirubins. Chem. Biol. 10, 1255-1266 (2003).
27. Polychronopoulos, P. et al. 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, 935-946 (2004).
28. Leost, M. et al. Paullones are potent inhibitors of glycogen synthase kinase-3β and cyclin-dependent kinase 5/p25. Eur. J. Biochem. 267, 5983-5994 (2000).
29. Meijer, L. et al. Inhibition of cyclin-dependent protein kinases, GSK-3β and CK1 by hymenialdisine, a marine sponge constituent. Chem. Biol. 7, 51-63 (1999).
30. Bain, J., McLauchlan, H., Elliott, M. & Cohen, P. The specificities of protein kinase inhibitors: an update. Biochem. J. 371, 199-204 (2003).
31. Phiel, C. J. & Klein, P. S. Molecular targets of lithium action. Annu. Rev. Pharmacol. Toxicol. 41, 789-913 (2001).
32. Kunick, C., Lauenroth, K., Leost, M., Meijer, L. & Lemcke, T. 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3β. Bioorg. Med. Chem. Lett. 14, 413-416 (2004).
33. Conde, S., Pérez, D. I., Martínez, A., Perez, C. & Moreno, F. J. Thienyl and phenyl α-halomethyl ketones: new inhibitors of glycogen synthase kinase (GSK-3β) from a library of compound searching. J. Med. Chem. 46, 4631-4633 (2003).
34. Cline, G. W. et al. Effects of a novel glycogen synthase kinase-3 inhibitor on insulin-stimulated glucose metabolism in Zucker Diabetic Fatty (fa/fa) rats. Diabetes 51, 2903-2910 (2003).
35. Ring D. B. et al. Selective glycogen synthase kinase-3 inhibitors potentiate insulin activation of glucose transport and utilisation in vitro and in vivo. Diabetes 52, 588-595 (2003).
36. Bhat, R. et al. Structural insights and bological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J. Biol. Chem. 278, 45937-45945 (2003).
37. Kuo, G.-H. et al. Synthesis and discovery of macrocyclic polyoxygenated bis-7-azaindolylmaleimides as a novel series of potent and highly selective glycogen synthase kinase-3β inhibitors. J. Med. Chem. 46, 4021-4031 (2003).
38. Bae, S. S., Cho,H., Mu, J. & Birnbaum, M. J. Isoform-specific regulation of insulin-dependent glucose uptake by Akt/protein kinase B. J. Biol. Chem. 278, 49530-49536 (2003).
39. MacAulay, K. et al. Use of lithium and SB-415286 to explore the role of glycogen synthase kinase-3 in the regulation of glucose transport and glycogen synthase. Eur. J. Biochem. 270, 3829-3838 (2003).
40. Lee, V. M.-Y., Goedert, M. & Trojanowski, J. Q. Neurodegenerative tauopathies. Annu. Rev Neurosci. 24, 1121-1159 (2001).
41. Annaert, W. & De Strooper, B. A cell biological perspective on Alzheimer's disease. Annu. Rev. Cell Dev. Biol. 18, 25-51 (2002).
42. Sun, X. et al. Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100. Neurosci. Lett. 321, 61-64 (2002).
43. Phiel, C. J., Wilson, C. A., Lee, V. M.-Y. & Klein, P. S. GSK-3α regulates production of Alzheimer's disease amyloid-β peptides. Nature 423, 435-439 (2003).
44. Ryder, J. et al. Divergent roles of GSK3 and CDK5 in APP processing. Biochem. Biophys. Res. Commun. 312, 922-929 (2003).
45. Goate, A et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704-706 (1991).
46. Sherrington, R. E. et al. (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754-760.
47. Levy-Lahad, E. W. et al. Candidate gene for the chromosone 1 familial Alzheimer's disease locus. Science 269, 970-973 (1995).
48. Rogaev, E. I. et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775-778 (1995).
49. Selkoe, D. J. & Schenk, D. Alzheimer's disease: Molecular understanding predicts amyloid-based therapeutics. Annu. Rev. Pharmacol. Toxicol. 43, 545-584 (2003).
50. Aplin, A E., Gibbs, G. M., Jacobsen, J. S., Gallo, J. M. & Anderton, B. H. In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3β. J. Neurochem. 67, 699-707 (1996).
51. Lee, M.-S. et al. (2003) APP processing is regulated by cytoplasmic phosphorylation. J. Cell Biol. 163, 83-95.
52. Poorkaj, P. et al. (1998) Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815-825.
53. Hutton, M. et al. (1998) Association of missense and 5′-splice site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702-705.
54. Spillantini, M. G. et al. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl. Acad. Sci. USA 95, 7737-7741 (1998).
55. Hanger, D. P., Hughes, K., Woodgett, J. R., Brion, J. P. & Anderton, B. H. Glycogen synthase Knase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase. Neurosci. Lett. 147, 58-62 (1992).
56. Mandelkow, E. M. et al. Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett. 314, 315-321 (1992).
57. Lovestone, S. et al. (1994) Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells. Curr. Biol. 4, 1077-1086.
58. Sperber, B. R., Leight, S., Goedert, M. & Lee, V. M.-Y. (1995) Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells. Neurosci. Lett. 197, 149-153.
59. Ishiguro, K. et al. Phosphorylation sites on tau by protein kinase I, a bovine-derived kinase generating an epitope of paired helical filaments. Neurosci. Lett. 148, 202-206 (1992).
60. Goedert, M. et al. Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer's disease: identification of phosphorylation sites in tau protein. Biochem. J. 301, 871-877 (1994).
61. Hasegawa, M. et al. Characterization of mAb AP422, a novel phosphorylation-dependent monoclonal antibody against tau protein. FEBS Lett. 384, 25-30 (1996).
62. Hong, M., Chen, D. C., Klein, P. S. & Lee, V. M.-Y. Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. J. Biol. Chem. 272, 25326-25332 (1997).
63. Munoz-Montano, J. R., Moreno, F. J., Avila, J. & Diaz-Nido, J. Lithium inhibits Alzheimer's disease-like tau protein phosphorylation in neurons. FEBS Lett. 411, 183-188 (1997).
64. Spittaels, K. et al. Glycogen synthase kinase-3β phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. J. Biol. Chem. 275, 41340-41349 (2000).
65. Lucas, J. J. et al. Decreased nuclear β-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3β conditional transgenic mice. EMBO J. 20, 27-39 (2001).
66. Jackson, G. R. et al. Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila. Neuron 34, 509-519 (2002).
67. Pérez, M., Hernández, F., Lim, F., Diaz-Nido & Avila, J. Chronic lithium treatment decreases mutant tau protein aggregation in a transgenic mouse model. J. Alzheimer's Res. 5, 301-308 (2003).
68. Lim, F., Hernández, F., Lucas, J. J., Gomez-Ramos, P., Moran, M. A. & Avila, J. (2001) FTDP-17 mutations in tau transgenic mice provoke lysosomal abnormalities and tau filaments in forebrain. Mol. Cell. Neurosci. 18, 702-714.
69. Lewis, J. et al. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nature Genet. 25, 402-405 (2000).
70. Allen, B. et al. Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein. J. Neurosci. 22, 9340-9351 (2002).
71. Hernández, F. et al. Glycogen synthase kinase-3 plays a crucial role in tau exon 10 splicing and intranuclear distribution of SC35. J. Biol. Chem. 279, 3801-3806 (2004).
72. The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72, 971-983 (1993).
73. Davies, S. W. et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90, 537-548 (1997).
74. Carmichael, J., Sugars, K. L., Bao, Y. P. & Rubinsztein, D. C. Glycogen synthase kinase-3β inhibitors prevent cellular polyglutamine toxicity caused by the Huntington's disease mutation. J. Biol. Chem. 277, 33791-33798 (2002).
75. Plotkin, B., Kaidanovich, O., Talior, I. & Eldar-Finkelman, H. Insulin mimetic action of synthetic phosphorylated peptide inhibitors of glycogen synthase kinase-3. J. Pharmacol. Exp. Therap. 305, 974-980 (2003).
76. Pap, M. & Cooper, G. M. Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway. J. Biol. Chem. 273, 19929-19932 (1998).
77. Cross, D. A. E. et al. Selective small molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. J. Neurochem. 77, 94-102 (2001).
78. Cade, J. Lithium salts in the treatment of psychotic excitement. Med. J. Aust. 2, 349-352 (1949).
79. Zhu, A. J. & Watt, F. M. β-Catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development 126, 2285-2298 (1999).
80. Davis, S. T. et al. Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors. Science 291, 134-137 (2001).
81. Polakis, P. Wnt signaling and cancer. Genes Dev. 14, 1837-1851 (2000).
82. Harada, N, et al. Intestinal polyposis in mice with a dominant stable mutation of the β-catenin gene. EMBO. J. 18, 5931-5942 (1999).
83. Morton, S., Davis, R. J., McLaren, A. & Cohen, P. A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun. EMBO J. 22, 3876-3886 (2003).
84. Cohen, Y. et al. Cancer morbidity in psychiatric patients: influence of lithium carbonate treatment. Med. Oncol. 15, 32-36 (1998).
85. Winder, W. W. & Hardie, D. G. AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am. J. Physiol. 277, E1-10 (1999).
86. Zhou, G. et al. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167-1174 (2001).
87. Wang, Z., Vogelstein, B. & Kinzler, K. W. Phosphorylation of β-catenin at S33, S37 or T41 can occur in the absence of phosphorylation of T45 in colon cancer cells. Cancer Res. 63, 5234-5235 (2003).