Download all structure-activity data for this target as a CSV file Description: Measured using GSK3 as a complex of and isozymes, isolated from pig brain 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 1 M and 10 M against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5 M 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 GSK3 plays an essential function in T cell differentiation and proliferation, and its activity is inhibited following antigen-driven T cell activation [6-7,27,32]. Recent evidence shows that in CD4+ T cells, inactivation of GSK3 is mediated by the GTPase GIMAP5 (GIMAP5; Q96F15), and that GIMAP5 represents an important checkpoint in T cell proliferation [34]. Ablation of Gimap5 activity leads to constitutive GSK3 activation and substantially reduced CD4+ T cell proliferation in vitro and in in vivo rodent models. A loss-of-function mutation in GIMAP5 has been identified in a patient with lymphopenia (see rs72650695; p.Leu204Pro). Treatment of this patient\'s T cells, ex vivo, with lithium chloride (a GSK3 inhibitor) rescues their proliferative potential. 1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR.(2011)Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. 2. Barker MD, Liddle J, Atkinson FL, Wilson DM, Dickson MC, Ramirez-Molina C, Lewis H, Davis RP, Somers DO, Neu M et al..(2018)Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. 3. Bebbington D, Binch H, Charrier JD, Everitt S, Fraysse D, Golec J, Kay D, Knegtel R, Mak C, Mazzei F et al..(2009)The discovery of the potent aurora inhibitor MK-0457 (VX-680). 4. 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. 5. Bertrand JA, Thieffine S, Vulpetti A, Cristiani C, Valsasina B, Knapp S, Kalisz HM, Flocco M.(2003)Structural characterization of the GSK-3beta active site using selective and non-selective ATP-mimetic inhibitors. 6. Beurel E, Kaidanovich-Beilin O, Yeh WI, Song L, Palomo V, Michalek SM, Woodgett JR, Harrington LE, Eldar-Finkelman H, Martinez A et al..(2013)Regulation of Th1 cells and experimental autoimmune encephalomyelitis by glycogen synthase kinase-3. 7. Beurel E, Yeh WI, Michalek SM, Harrington LE, Jope RS.(2011)Glycogen synthase kinase-3 is an early determinant in the differentiation of pathogenic Th17 cells. 8. Bhat R, Xue Y, Berg S, Hellberg S, Ormö M, Nilsson Y, Radesäter AC, Jerning E, Markgren PO, Borgegård T et al..(2003)Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. 9. Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G et al..(2013)Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. 10. Coffman K, Brodney M, Cook J, Lanyon L, Pandit J, Sakya S, Schachter J, Tseng-Lovering E, Wessel M.(2011)6-amino-4-(pyrimidin-4-yl)pyridones: novel glycogen synthase kinase-3β inhibitors. 11. 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. 12. 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. 13. Ding S, Wu TY, Brinker A, Peters EC, Hur W, Gray NS, Schultz PG.(2003)Synthetic small molecules that control stem cell fate. 14. Domínguez JM, Fuertes A, Orozco L, del Monte-Millán M, Delgado E, Medina M.(2012)Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. 15. Dowling JE, Chuaqui C, Pontz TW, Lyne PD, Larsen NA, Block MH, Chen H, Su N, Wu A, Russell D et al..(2012)Potent and Selective Inhibitors of CK2 Kinase Identified through Structure-Guided Hybridization. 16. 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. 17. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S.(2007)A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. 18. Feldman RI, Wu JM, Polokoff MA, Kochanny MJ, Dinter H, Zhu D, Biroc SL, Alicke B, Bryant J, Yuan S et al..(2005)Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1. 19. 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. 20. 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. 21. 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. 22. Jiang X, Zhao B, Britton R, Lim LY, Leong D, Sanghera JS, Zhou BB, Piers E, Andersen RJ, Roberge M.(2004)Inhibition of Chk1 by the G2 DNA damage checkpoint inhibitor isogranulatimide. 23. Jiang XY, Chen TK, Zhou JT, He SY, Yang HY, Chen Y, Qu W, Feng F, Sun HP.(2018)Dual GSK-3β/AChE Inhibitors as a New Strategy for Multitargeting Anti-Alzheimer\'s Disease Drug Discovery. 24. Kunick C, Lauenroth K, Leost M, Meijer L, Lemcke T.(2004)1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. 25. Leclerc S, Garnier M, Hoessel R, Marko D, Bibb JA, Snyder GL, Greengard P, Biernat J, Wu YZ, Mandelkow EM et al..(2001)Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer\'s disease. A property common to most cyclin-dependent kinase inhibitors?. 26. Leost M, Schultz C, Link A, Wu YZ, Biernat J, Mandelkow EM, Bibb JA, Snyder GL, Greengard P, Zaharevitz DW et al..(2000)Paullones are potent inhibitors of glycogen synthase kinase-3beta and cyclin-dependent kinase 5/p25. 27. Lovatt M, Bijlmakers MJ.(2010)Stabilisation of β-catenin downstream of T cell receptor signalling. 28. 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. 29. Menichincheri M, Bargiotti A, Berthelsen J, Bertrand JA, Bossi R, Ciavolella A, Cirla A, Cristiani C, Croci V, D\'Alessio R et al..(2009)First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. 30. Naerum L, Nørskov-Lauritsen L, Olesen PH.(2002)Scaffold hopping and optimization towards libraries of glycogen synthase kinase-3 inhibitors. 31. O\'Neill DJ, Shen L, Prouty C, Conway BR, Westover L, Xu JZ, Zhang HC, Maryanoff BE, Murray WV, Demarest KT et al..(2004)Design, synthesis, and biological evaluation of novel 7-azaindolyl-heteroaryl-maleimides as potent and selective glycogen synthase kinase-3beta (GSK-3beta) inhibitors. 32. Ohteki T, Parsons M, Zakarian A, Jones RG, Nguyen LT, Woodgett JR, Ohashi PS.(2000)Negative regulation of T cell proliferation and interleukin 2 production by the serine threonine kinase GSK-3. 33. 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. 34. Patterson AR, Endale M, Lampe K, Aksoylar HI, Flagg A, Woodgett JR, Hildeman D, Jordan MB, Singh H, Kucuk Z et al..(2018)Gimap5-dependent inactivation of GSK3β is required for CD4+ T cell homeostasis and prevention of immune pathology. 35. 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. 36. 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. 37. Ryves WJ, Harwood AJ.(2001)Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. 38. 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. 39. Shen W, Taylor B, Jin Q, Nguyen-Tran V, Meeusen S, Zhang YQ, Kamireddy A, Swafford A, Powers AF, Walker J et al..(2015)Inhibition of DYRK1A and GSK3B induces human β-cell proliferation. 40. Sivaprakasam P, Han X, Civiello RL, Jacutin-Porte S, Kish K, Pokross M, Lewis HA, Ahmed N, Szapiel N, Newitt JA et al..(2015)Discovery of new acylaminopyridines as GSK-3 inhibitors by a structure guided in-depth exploration of chemical space around a pyrrolopyridinone core. 41. Tantray MA, Khan I, Hamid H, Alam MS, Umar S, Ali Y, Sharma K, Hussain F.(2016)Synthesis of Novel Oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles as Glycogen Synthase Kinase-3β Inhibitors with Anti-inflammatory Potential. 42. ter Haar E, Coll JT, Austen DA, Hsiao HM, Swenson L, Jain J.(2001)Structure of GSK3beta reveals a primed phosphorylation mechanism. 43. Werstuck GH, Kim AJ, Brenstrum T, Ohnmacht SA, Panna E, Capretta A.(2004)Examining the correlations between GSK-3 inhibitory properties and anti-convulsant efficacy of valproate and valproate-related compounds. 44. 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. 45. Zhang P, Hu HR, Huang ZH, Lei JY, Chu Y, Ye DY.(2012)Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3β inhibitors through virtual screening. GSK subfamily: glycogen synthase kinase 3 beta. Last modified on 21/02/2020. Accessed on 18/05/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2030.

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