English
往期目录
新闻公告
More
化学进展 2007, Vol. 19 Issue (04): 614-623 前一篇   后一篇

• 综述与评论 •

GSK-3抑制剂研究进展*

张娜1;蒋勇军2**;俞庆森1;邹建卫2   

  1. 1. 浙江大学 化学系 杭州 310027;
    2. 浙江大学宁波理工学院 分子设计与营养工程市重点实验室 宁波 315104
  • 收稿日期:2006-05-18 修回日期:2006-07-10 出版日期:2007-04-24 发布日期:2007-04-24
  • 通讯作者: 蒋勇军
下载PDF ( 1652 ) 引用
导出

Studies of Glycogen Synthase Kinase-3 Inhibitors

Zhang Na1;Jiang Yongjun2**; Yu Qingsen1 ;Zou Jianwei2   

  1. 1. Department of Chemistry, Zhejiang University, Hangzhou 310027, China;
    2. Key Laboratory for Molecular Design and Nutrition Engineering of Ningbo City, Ningbo Institute of Technology, Ningbo 315104, China
  • Received:2006-05-18 Revised:2006-07-10 Online:2007-04-24 Published:2007-04-24
  • Contact: Jiang Yongjun
糖原合成酶激酶-3 (Glycogen synthase kinase-3, GSK-3)是一个多功能的丝氨酸/苏氨酸蛋白激酶，不仅参与肝糖代谢过程，而且还参与Wnt和Hedgehog信号通路，通过磷酸化多种底物蛋白来调节细胞的生理过程。GSK-3抑制剂作为目前倍受关注的小分子抑制剂，对治疗神经退化性疾病，癌症，II型糖尿病具有潜在的疗效。本文针对已开发出的GSK-3抑制剂,对其结构,与蛋白的作用模式以及构效关系进行阐述，为进一步设计合理的药物先导化合物和特异性小分子化学探针提供有益的启示。
关键词： GSK-3, 抑制剂, 构效关系, 选择性, 药物设计
Glycogen synthase kinase-3 (GSK-3)，a multifunctional serine-threonine kinase, has played an important role in glycogen metabolism and is known to occupy a central stage in many cellular physiological events by phosphorylation of multifold substrate proteins, including Wnt and Hedgehog signal transduction pathways. Small molecular inhibitors of GSK-3, as new promising drugs for the treatment of neurodegenerative diseases, cancer and type II diabetes, are getting more and more attentions. Information gained from their structures, binding modes and structure-activity relationships provides some clues for the future optimization of drug lead-compounds and selective chemical probes .
Key words: GSK-3, inhibitors, structure-activity relationship, selectivity, drug design

中图分类号: 

()

[ 1 ] Ali A , Hoeflich K P , Woodgett J R1 Chem1 Rev. , 2001 , 101 :2527 —2540
[ 2 ] Grimes C A , Jope R S. Prog. Neurobiol . , 2001 , 65 : 391 —426
[ 3 ] Eldar-Finkelman H. Trends. Mol . Med. , 2002 , 8 : 126 —132
[ 4 ] Castro A , Martinez A. Exp. Opin. Ther. Pat . , 2000 , 10 :1519 —1527
[ 5 ] Kim L , Kimmel A R. Curr. Opin. Genet . Dev. , 2000 , 10 :508 —514
[ 6 ] Wagman A S , Nuss J M. Curr. Pharm. Design. , 2001 , 7 :417 —450
[ 7 ] Hoeflich K P , Luo J , Rubie E A , et al . Nature , 2000 , 406 :86 —90
[ 8 ] Dajani R , Fraser E , Roe S M, et al . Cell , 2001 , 105 : 721 —732
[ 9 ] Ter Haar E , Coll J T , Austen D A , et al . Nat . Struct . Biol . ,2001 , 8 : 593 —596
[10] Brown N R , Noble M E , Endicott J A. Nature Cell Biol . , 1999 ,1 : 438 —443
[11] Bellon S , Fitzgibbon M J , Fox T , et al . Structure Fold. Des. ,1999 , 7 : 1057 —1065
[12] Meijer L , Flajoet M, Greengard P. Trends Pharmacol . Sci . ,2004 , 26 : 471 —480
[13] Hagen T , Vidal-Puig A. Biochem. Biophy. Res. Co. , 2002 ,294 : 324 —328
[14] Fluhrer R , Friedlein A , Haass C , et al . J . Biol . Chem. , 2004 ,279 : 1585 —1593
[15] Fiol C J , Wang A , Roeske R W, Roach P J . J . Biol . Chem. ,1990 , 265 : 6061 —6065
[16] Ikeda S , Kishida S , Yamamoto H , Murai H , Koyama S , et al .EMBO J . , 1998 , 17 : 1371 —1384
[17] Knockaert M, Greengard P , Meijer L. Trends Pharmacol . Sci . ,2002 , 23 : 417 —425
[18] Schultz C , Link A , Leost M, Zaharevitz D , et al . J . Med.Chem. , 1999 , 42 : 2909 —2919
[19] Leost M, Schultz C , Link A , Wu YZ , et al . Eur. J . Biochem. ,2000 , 267 : 5983 —5994
[20] Gussio R , Zaharevitz D W, Mcgrath C F , et al . Anticancer Drug Des. , 2000 , 15 : 53 —66
[21] Bain J , Lauchlan H M, Elliot M, Cohen P. Biochem. J . , 2003 ,371 : 199 —204
[22] Kunick C , Lauenroth K, Leost M, et al . Bioorg. Med. Chem.Lett . , 2004 , 14 : 413 —416
[23] Berstrand J A , Thieffine S , Vulpetti A , Cristiani C , et al . J .Mol . Biol . , 2003 , 333 : 393 —407
[24] Kunick C , Lauenroth K, Wieking K, Xie X. J . Med. Chem. ,2004 , 47 : 22 —36
[25] Damiens E , Baratte B , Marie D , Eisenbrand G, Meijer L.Oncogene. , 2001 , 20 : 3786 —3797
[26] Leclerc S , Garnier M, Hoessel R , et al . J . Biol . Chem. , 2001 ,276 : 251 —260
[27] Hoessel R , Leclerc S , Endicott J A , et al . Nat . Cell Biol . ,1999 , 1 : 60 —67
[28] Polychronopoulos P , Skaltsounis A L , Magiatis P , et al . J . Med.Chem. , 2004 , 47 : 935 —946
[29] Meijer L , Skaltsounis A L , Magiatis P , et al . Chem. Biol . ,2003 , 10 : 1255 —1266
[30] Hughes K, Nikolakaki E , Plyte S E , et al . EMBOJ . , 1993 , 12 :803 —808
[31] Zhang N , Jiang Y J , Zou J W, et al . Eur. J . Med. Chem. ,2006 , 41 : 373 —378
[32] Zhang H C , White K B , Ye H , et al . Bioorg. Med. Chem.Lett . , 2003 , 13 : 3049 —3053
[33] Hers I , TavaréJ M, Denton R M. FEBS Lett . , 1999 , 460 :433 —436
[34] Toullec D , Pianetti P , Coste H , et al . J . Biol . Chem. , 1991 ,266 : 15771 —15781
[35] Alessi D R. FEBS Lett . , 1997 , 402 : 121 —123
[36] Standaert M L , Bandyopadhyay G, Antwi E K, Farese R V.Endocrinology , 1999 , 140 : 2145 —2151
[37] Cook D , Fry M J , Hughes K, et al . EMBO J . , 1996 , 15 :4526 —4536
[38] Boyle W J , Smeal T , Defize L H K, Angel P , Woodgett J R ,Karin M, Hunter T. Cell , 1991 , 64 : 573 —584
[39] Kuo G H , Prouty C , DeAngelis A , et al . J . Med. Chem. ,2003 , 46 : 4021 —4031
[40] Shen L , Prouty C , Conway B R , et al . Bioorg. Med. Chem. ,2004 , 12 : 1239 —1255
[41] Coghlan M P , Culbert A A , Cross D A E , et al . Chem. Biol . ,2000 , 7 : 793 —803
[42] Carlsen J , Christiansen K, Vinten J . Cell . Signal . , 1997 , 9 :447 —450
[43] Lawrence J C , Roach P J . Diabetes , 1997 , 46 : 541 —547
[44] Bosch F , Gomez-Foix A M, Arino J , Guinovart J J . J . Biol .Chem. , 1986 , 261 : 16927 —16931
[45] Smith D G, Buffet M, Fenwick A E , et al . Bioorg. Med. Chem.Lett . , 2001 , 11 : 635 —639
[46] Lescot E , Bureau R , Santos J S D , et al . J . Chem. Inf .Model . , 2005 , 45 : 708 —715
[47] Ring D B , Johnson K W, Henriksen EJ , et al . Diabetes , 2003 ,52 : 588 —595
[48] Wagman A S , Johnson K W, Bussiere D E. Curr. Pharm.Design , 2004 , 10 : 1105 —1137
[49] Peat A J , Garrido D , Boucheron J A , Schweiker S L , et al .Bioorg. Med. Chem. Lett . , 2004 , 14 : 2127 —2130
[50] Smalley T L , Peat A J , Boucheron J A , et al . Bioorg. Med.Chem. Lett . , 2006 , 16 : 2091 —2094
[51] Tavares F X, Boucheron J A , Dickerson S H , et al . J . Med.Chem. , 2004 , 47 : 4716 —4730
[52] Witherington J , Bordas V , Haigh D , et al . Bioorg. Med. Chem.Lett . , 2003 , 13 : 1581 —1584
[53] Witherington J , Bordas V , Garland S L , et al . Bioorg. Med.Chem. Lett . , 2003 , 13 : 1577 —1580
[54] Witherington J , Bordas V , Gaiba A , et al . Bioorg. Med. Chem.Lett . , 2003 , 13 : 3055 —3057
[55] Witherington J , Bordas V , Gaiba A , et al . Bioorg. Med. Chem.Lett . , 2003 , 13 : 3059 —3062
[56] Mettey Y, Gompel M, Thomas V , et al . J . Med. Chem. , 2003 ,46 : 222 —236
[57] Schulze-Gahmen U , Brandsen J , Jones H D , et al . Proteins :Struct . Funct . Genet . , 1995 , 22 : 378 —391
[58] De Azevedo W F , Leclerc S , Meijer L , et al . Eur. J . Biochem. ,1997 , 243 : 518 —526
[59] Morgan D O , Kim S H. Nature , 1993 , 363 : 595 —602
[60] Zeng M, Jiang Y J , Zhang B , et al . Bioorg. Med. Chem. Lett . ,2005 , 15 : 395 —399
[61] Wan Y, Hur W, Cho C Y, et al . Chem. Biol . , 2004 , 11 :247 —259
[62] Breton J J , Chabot-Fletcher M C. J . Pharmacol . Exp. Ther. ,1997 , 282 : 459 —466
[63] Meijer L , Thunnissen A M W H , White W H , et al . Chem.Biol . , 2000 , 7 : 51 —63
[64] Tasdemir D , Mallon R , Greenstein M, et al . J . Med. Chem. ,2002 , 45 : 529 —532
[65] Olesen P H , S? rensen A R , Urs? B , et al . J . Med. Chem. ,2003 , 46 : 3333 —3341
[66] Bhat R , Xue Y F , Berg S , et al . J . Biol . Chem. , 2003 , 278 :45937 —45945
[67] Pande V , Ramos M J . Bioorg. Med. Chem. Lett . , 2005 , 15 :5129 —5135
[68] Richardson C M, Williamson D S , Parratt M J , et al . Bioorg.Med. Chem. Lett . , 2006 , 16 : 1353 —1357
[69] Abadi A H , Abou-Seri S M, Abdel-Rahman D E , et al . Eur. J .Med. Chem. , 2006 , 41 : 296 —303
[70] Sondhi S M, Singh N , Kumar A , et al . Bioorg. Med. Chem.Lett . , 2006 , 14 : 3758 —3765
[71] Hong M, Chen D C , Klein P S , Lee V M. J . Biol . Chem. ,1997 , 272 : 25326 —25332
[72] Mu? noz-Monta? no J R , Moreno F J , Avila J , Diaz2Nido J . FEBS Lett . , 1997 , 411 : 183 —188
[73] Klein P S , Melton D A. Proc. Natl . Acad. Sci . USA , 1996 ,93 : 8455 —8459
[74] Ryves WJ , Harwood A J . Biochem. Biophys. Res. Commun. ,2001 , 280 : 720 —725
[75] De Sarno P , Li X H , Jope R S. Neuropharmacology , 2002 , 43 :1158 —1164
[76] Chalecka-Franaszek E , Chuang D M. Proc. Natl . Acad. Sci .USA , 1999 , 96 : 8745 —8750
[77] Alvarez G, Mu? noz-Monta? no J R , Satrustegui J , et al . FEBS Lett . , 1999 , 453 : 260 —264
[78] Martinez A , Alonso M, Castro A , et al . J . Med. Chem. , 2002 ,45 : 1292 —1299
[79] Kaugars G, Atherton J P , Han F. J . Org. Chem. , 1992 , 57 :1671 —1676
[80] Martinez A , Castro A , Perez C , et al . WO 01P85 685 , 2001
[81] Martinez A , Alonso M, Castro A , et al . J . Med. Chem. , 2005 ,48 : 7103 —7112
[82] Cohen M, Zhang C , Shokat K, et al . Science , 2005 , 308 :1318 —1320
[83] Lustig B , Behrens J . J . Cancer Res. Clin. Oncol . , 2003 , 129 :199 —221
[84] Polakis P. Genes Dev. , 2000 , 14 : 1837 —1851
[85] Cohen P , Frame S. Nat . Rev. Mol . Cell Biol . , 2001 , 2 : 769 —776
[86] Frame S , Cohen P , Biondi R M. Mol . Cell , 2001 , 7 : 1321 —1327
[87] Rothenberg M, Carbone D , Johnson D. Nat . Rev. Cancer ,2003 , 3 : 303 —309
[1] 李帅, 朱娜, 程扬健, 陈缔. NH3选择性催化还原NOx的铜基小孔分子筛耐硫性能及再生研究[J]. 化学进展, 2023, 35(5): 771-779.
[2] 王芷铉, 郑少奎. 选择性离子吸附原理与材料制备[J]. 化学进展, 2023, 35(5): 780-793.
[3] 朱国辉, 还红先, 于大伟, 郭学益, 田庆华. 废旧锂离子电池选择性提锂[J]. 化学进展, 2023, 35(2): 287-301.
[4] 蒋茹, 刘晨旭, 杨平, 游书力. 手性催化与合成中的一些凝聚态化学问题[J]. 化学进展, 2022, 34(7): 1537-1547.
[5] 杨世迎, 范丹阳, 保晓娟, 傅培瑶. 碳材料修饰零价铝的作用机制[J]. 化学进展, 2022, 34(5): 1203-1217.
[6] 管可可, 雷文, 童钊明, 刘海鹏, 张海军. MXenes的制备、结构调控及电化学储能应用[J]. 化学进展, 2022, 34(3): 665-682.
[7] 张柏林, 张生杨, 张深根. 稀土元素在脱硝催化剂中的应用[J]. 化学进展, 2022, 34(2): 301-318.
[8] 张巍, 谢康, 汤云灏, 秦川, 成珊, 马英. 过渡金属基MOF材料在选择性催化还原氮氧化物中的应用[J]. 化学进展, 2022, 34(12): 2638-2650.
[9] 白文己, 石宇冰, 母伟花, 李江平, 于嘉玮. Cs2CO3辅助钯催化X—H (X=C、O、N、B)官能团化反应的理论计算研究[J]. 化学进展, 2022, 34(10): 2283-2301.
[10] 宋路杰, 吴友平, 邓建平. 手性药物的对映体选择性释放[J]. 化学进展, 2021, 33(9): 1550-1559.
[11] 程丽丽, 章赟, 朱烨坤, 吴瑛. 选择性氧化HMF[J]. 化学进展, 2021, 33(2): 318-330.
[12] 王欣瑜, 赵富平, 张儒, 孙子茹, 刘胜男, 高清志. 抗肿瘤缺氧诱导因子-1的小分子抑制剂[J]. 化学进展, 2021, 33(12): 2259-2269.
[13] 冯勇, 李谕, 应光国. 基于过硫酸盐活化的微界面电子转移氧化技术[J]. 化学进展, 2021, 33(11): 2138-2149.
[14] 顾凯丽, 李浩贞, 张晋华, 李锦祥. 硫化零价铁去除水中污染物的效能及交互机制[J]. 化学进展, 2021, 33(10): 1812-1822.
[15] 武江洁星, 魏辉. 浅谈纳米酶的高效设计策略[J]. 化学进展, 2021, 33(1): 42-51.
阅读次数
全文


摘要

GSK-3抑制剂研究进展*