Structural Insights and Biological Effects of Glycogen Synthase Kinase 3-specific Inhibitor AR-A014418
Ratan Bhat,Yafeng Xue,Stefan von Berg,Sven Hellberg,Mats Ormö,Yvonne Nilsson,Ann-Cathrin Radesäter,Eva Jerning,Per-Olof Markgren,Thomas Borgegård,Martin Nylöf,Alfredo Giménez-Cassina,Félix Hernández,José J. Lucas,Javier Díaz-Nido,Jesús Avila +15 more
TLDR
AR-A014418 is the first compound of a family of specific inhibitors of GSK3 that does not significantly inhibit closely related kinases such as cdk2 or cdk5 and may have important applications as a tool to elucidate the role of Gsk3 in cellular signaling and possibly in Alzheimer's disease.About:
This article is published in Journal of Biological Chemistry.The article was published on 2003-11-14 and is currently open access. It has received 487 citations till now. The article focuses on the topics: GSK-3 & ASK1.read more
Citations
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The selectivity of protein kinase inhibitors: a further update.
Jenny Bain,Lorna Plater,Matthew Elliott,Natalia Shpiro,C. James Hastie,Hilary McLauchlan,Iva V. Klevernic,J. Simon C. Arthur,Dario R. Alessi,Philip Cohen +9 more
TL;DR: Harmine has been identified as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro and the results have further emphasized the need for considerable caution in using small-molecule inhibitors of protein kinases to assess the physiological roles of these enzymes.
Journal ArticleDOI
GSK-3-Selective Inhibitors Derived from Tyrian Purple Indirubins
Laurent Meijer,Alexios-Leandros Skaltsounis,Prokopios Magiatis,Panagiotis Polychronopoulos,Marie Knockaert,Maryse Leost,Xiaozhou P. Ryan,Claudia Alin Vonica,Ali H. Brivanlou,Rana Dajani,Claudia Crovace,Cataldo Tarricone,Andrea Musacchio,S. Mark Roe,Laurence H. Pearl,Paul Greengard +15 more
TL;DR: 6-bromoindirubins provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3, and closely mimicked Wnt signaling in Xenopus embryos.
Journal ArticleDOI
GSK3 inhibitors: development and therapeutic potential
Philip Cohen,Michel Goedert +1 more
TL;DR: The biology of GK3 relevant to its potential as a target for diabetes and neurodegenerative diseases is described, and progress in the development of GSK3 inhibitors is discussed.
Journal ArticleDOI
Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo
Wendy Noble,Emmanuel Planel,Cindy Zehr,Vicki Olm,Jordana L Meyerson,Farhana Suleman,Kate Gaynor,Lili Wang,John LaFrancois,Boris Feinstein,Mark P. Burns,Pavan Krishnamurthy,Yi Wen,Ratan Bhat,Jada Lewis,Dennis W. Dickson,Karen Duff +16 more
TL;DR: Results support the idea that kinases are involved in tauopathy progression and that kinase inhibitors may be effective therapeutically and that lithium exerts its effect through GSK-3 inhibition.
Journal ArticleDOI
Pharmacological inhibitors of glycogen synthase kinase 3
TL;DR: A large body of evidence supports speculation that pharmacological inhibitors of GSK-3 could be used to treat several diseases, including Alzheimer's disease and other neurodegenerative diseases, bipolar affective disorder, diabetes, and diseases caused by unicellular parasites that express G SKS-3 homologues.
References
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PROCHECK: a program to check the stereochemical quality of protein structures
TL;DR: The PROCHECK suite of programs as mentioned in this paper provides a detailed check on the stereochemistry of a protein structure and provides an assessment of the overall quality of the structure as compared with well refined structures of the same resolution.
Journal ArticleDOI
Neuropathological stageing of Alzheimer-related changes.
Heiko Braak,Eva Braak +1 more
TL;DR: The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations, permitting the differentiation of six stages.
Journal ArticleDOI
Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.
TL;DR: The analysis described shows K I does not equal I 50 when competitive inhibition kinetics apply; however, K I is equal to I 50 under conditions of either noncompetitive or uncompetitive kinetics.
Journal ArticleDOI
Specificity and mechanism of action of some commonly used protein kinase inhibitors
TL;DR: The results demonstrate that the specificities of protein kinase inhibitors cannot be assessed simply by studying their effect on kinases that are closely related in primary structure, and proposes guidelines for the use of protein Kinase inhibitors in cell-based assays.
Journal ArticleDOI
A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).
TL;DR: One such compound, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, LY294002, completely and specifically abolished PtdIns 3-kinase activity, which may be beneficial in the treatment of proliferative diseases as well as in elucidating the biological role of the kinase in cellular proliferation and growth factor response.
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