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Hsp90抑制剂的研究进展 被引量：23

Recent progress in the study of Hsp90 inhibitors
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摘要 热休克蛋白90(Hsp90)是生物进化过程中高度保守的一类蛋白,作为分子伴侣对细胞中众多信号蛋白的构象成熟和功能稳定进行调控。近年来的研究证明,Hsp90与肿瘤发生、发展、生物学行为及其预后有密切的关系,已成为新兴的抗肿瘤药物作用靶点,众多Hsp90抑制剂应运而生,同时基于结构的小分子抑制剂的设计也引起日益广泛的关注,本文就Hsp90的结构特点及其相关抑制剂进行综述,以期对Hsp90抑制剂的发现和优化提供依据。 Heat shock protein 90 （Hsp90） is a highly conserved chaperone that is responsible for the maturation and activity of a variety of signaling proteins. Hsp90 has become the target of antitumor drugs because of its close relationship with occurrence and development, biological behavior and prognosis of tumor. Many Hsp90 inhibitors have emerged, and interests have arisen around structure-based design of small molecules. In this review, we illustrate the structure features and related inhibitors aiming at discovering and optimizing Hsp90 inhibitors.
作者 孟帅 山广志 李卓荣
机构地区 中国医学科学院北京协和医学院医药生物技术研究所
出处 《中国抗生素杂志》 CAS CSCD 北大核心 2011年第4期241-248,共8页 Chinese Journal of Antibiotics
基金 "863"计划课题项目(2006AA02Z414) 重大新药创制重大专项(2009ZX09301-003)
关键词 HSP90 抑制剂 基于结构的药物设计 Hsp90 Inhibitors Structure-based drug design
分类号 R979.19 [医药卫生—药品]
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参考文献27

  • 1Maloney A, Workman P. HSP90 as a new therapeutic target for cancer therapy: the story unfolds[J]. Expert Opin Biol Ther, 2002, 2(1): 3-24.
  • 2胡秀娟,王雪峰.HSP90在肿瘤中的研究[J].医学综述,2008,14(1):67-69. 被引量：14
  • 3Stebbins C E, Russo A A, Schneider C, et al. Crystal structure of an Hsp90-geldanamycin complex; targeting of a protein chaperone by an antitumor agent[J]. Cell, 1997, 89(2): 239-250.
  • 4Bergerat A, De-Massy B, Gadelle D, et al. An atypical toposomeerase II from Archaea with implications for meiotic recombination[J]. Nature, 1997, 386(6623): 414-417.
  • 5Obermann W M, Sondermann H, Russo A A, et al. In vivofunction of hsp90 is dependent on ATP binding and ATP hydrolysis[J]. J CellBiol, 1998, 143(4): 901-910.
  • 6Meyer P, Prodromou C, Hu B, et al. Structural and functional analysis of the middle segment of hsp90: implications for ATP hydrolysis and client protein and cochaperone interactions[J]. Mol Cell, 2003, 11(3): 647-658.
  • 7Harris S F, Shiau A K, Agard D A. The crystal structure of the earboxy-terminal dimerization domain of htpG, the Escherichia coli Hsp90, reveals a potential substrate binding site[J]. Structure, 2004, 12(6): 1087-1097.
  • 8Langer T, Schlatter H, Fasold H. Evidence that the novobiocin-sensitive ATP-binding site of the heat shock protein 90(HSP90) is necessary for its autophosphorylation[J]. Cell Biol lnt, 2002, 26(7): 653-657.
  • 9Ochel H J, Schulte T W, Nguyen P, et al. The benz0quinone ansamycin geldanamycin stimulates proteolytic degradation of focal adhesion kinase[J]. Mol Genet Metab, 1999, 66(1): 24-30.
  • 10Roe S M, Prodromuu C, O'brien R, et al. Structural basis for inhibition of the Hsp90 molecular chaPerone by the antitumor antibiotics radiciol and geldanamycin[J]. J Med Chem, 1999, 42(2): 260-266.

二级参考文献20

  • 1Rutherford SL, Lindquist S. HSP90 as a capacitor for morphological evolution [ J ]. Nature, 1998,396(6709) : 336-342.
  • 2Pandey P, Saleh A, Nakazawa A, et al. Negative regulation of cytoehrome c-mediated oligomefization of Apaf-land activation of proeaspase-9 by heat shock protein 90 [ J ]. EMBO J, 2000, 19 ( 16 ) : 4310- 4322.
  • 3Nimmanapalli R, O' Bryan E, Bhalla K. Geldanamycin and its analogue 17-allylamino- 17-demethoxygeldanamycin lowers Bcr-Abl levels and induces apoptosis and differentiation of Bcr-Abl-positive human leukemic blasts[J]. Cancer Res,2001,61(5) : 1799-1804.
  • 4Blagosklonny MV, Toretsky J, Bohen S, et al. Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90[J]. Proe Natl Acad Sci USA, 1996,93(16) :8379-8383.
  • 5Shiono Y, Fujita Y, Oka S, et al. ATPase inhibitors suppress actinomycin D-induced apoptosis in leukemia cells[J]. Anticancer Res,2002,22 (5) :2907-2911.
  • 6Zhao C, Wang EH. Heat shock protein 90 suppresses tumornecrosis factorα induced apoptosis by preventing thecleavage of Bid in NIH3T3 fibroblasts[ J]. Cell Signal,2004,16(3 ) :313-321.
  • 7Yano M,Naito Z,Tanaka S, et al. Expression and roles of heat shock proteins in human breast cancer[J]. Jpn J Cancer Res, 1996,87(9) : 908-915.
  • 8Gress TM, Muller-Pillasch F, Weber C, et al. Diferential expression of heat shock proteins in pancreatic carcinoma [ J ]. Cancer Res, 1994,54 (2) :547-551.
  • 9Udono H, Srivastava PK. Heat shock protein 70-associated peptides elicit specific cancer immunity[J]. J Exp Med, 1993, 178(4) : 1391- 1396.
  • 10Srivastava PK. Immunotherapy for human cancer using heat shock protein-peptide complexes[J]. Curr Oncol Rep,2005,7(2) : 104-108.

共引文献13

同被引文献229

引证文献23

二级引证文献49

中国抗生素杂志
2011年 第4期

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