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肿瘤坏死因子受体选择性拮抗剂的研究进展

江海龙 王宁远 陆一鸣

江海龙, 王宁远, 陆一鸣. 肿瘤坏死因子受体选择性拮抗剂的研究进展[J]. 药学实践与服务, 2015, 33(5): 392-395. doi: 10.3969/j.issn.1006-0111.2015.05.003
引用本文: 江海龙, 王宁远, 陆一鸣. 肿瘤坏死因子受体选择性拮抗剂的研究进展[J]. 药学实践与服务, 2015, 33(5): 392-395. doi: 10.3969/j.issn.1006-0111.2015.05.003
JIANG Hailong, WANG Ningyuan, LU Yiming. Research advance of selective inhibitor of tumornecrosis factor receptor[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(5): 392-395. doi: 10.3969/j.issn.1006-0111.2015.05.003
Citation: JIANG Hailong, WANG Ningyuan, LU Yiming. Research advance of selective inhibitor of tumornecrosis factor receptor[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(5): 392-395. doi: 10.3969/j.issn.1006-0111.2015.05.003

肿瘤坏死因子受体选择性拮抗剂的研究进展

doi: 10.3969/j.issn.1006-0111.2015.05.003
基金项目: 国家自然科学基金(30500093);国家科技部"重大新药创制"专项(2009ZX09103-690);上海市科委重点项目(04JC14002);军队"十一五"计划(06Q042);上海市高校优秀青年教师科研专项基金(ejd09011)

Research advance of selective inhibitor of tumornecrosis factor receptor

  • 摘要: 肿瘤坏死因子(TNF)信号通路是很有价值的治疗靶标,抗TNF药物已成功治疗自身免疫和炎症疾病,但传统的抗TNF药物完全封闭TNF信号通路,导致影响自身的免疫调节和监视功能而增加感染、致癌的风险和产生新的自身免疫疾病。选择性抑制sTNF/TNFR1而保留mTNF/TNFR2传导的信号能减少副作用而不降低治疗效果。该文探讨了选择性抑制TNFR1介导的信号通路对治疗TNF相关疾病的意义,分析TNF识别并激活肿瘤坏死因子受体(TNFR)的作用机制,可能会为设计新药提供新的思路。
  • [1] Apostolaki M, Armaka M, Victoratos P,et al.Cellular mechanisms of TNF function in models of inflammation and autoimmunity[J].Curr Dir Autoimmun, 2010,11(2):1-26.
    [2] Mukai Y,Nakamura T, Yoshikawa M,et al. Solution of the structure of the TNF-TNFR2 complex[J]. Sci Signal,2010,3 (148): 1-10.
    [3] Hehlgans T, Pfeffer K. The intriguing biology of the tumounecrosis factor/tumour necrosis factor receptor superfamily players,rules and the games[J].Immunology,2005,115(1):1-20.
    [4] Mcllwain DR,Lang PA,Maretzky T,et al.IRhom2 regulation of TACE controls TNF-mediated protection against listeria and responses to LPS[J].Science,2012,335(6065):229-232.
    [5] Chen X, Wu X, Zhou Q,et al.TNFR2 is critical for the stabilization of the CD4+Foxp3+ Regulatory T cell phenotype in the inflammatory environmentl[J]. J Immuno,2013, 190(3):1076-1084.
    [6] Faustman D, Davis M. TNF receptor 2 pathway: drug target for autoimmune diseases[J].Nat Rev Drug Discov, 2010, 9(6):482-493.
    [7] Magis C, van der Sloot AM, Serrano L,et al. An improved understanding of TNFL/TNFR interactions using structure-based classi cations[J].Trends Biochem Sci,2012,37(9):353-363.
    [8] Dixon,Hyrich KL, Watson KD,et al. Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR)[J]. Ann Rheum Dis,2010,69(3):522-528.
    [9] Takeuchi T, Tatsuki Y, NogamiY,et al. Post marketing surveillance of the safety profile of infliximab in 5 000 Japanese patients with rheumatoid arthritis[J].Ann Rheum Dis,2008, 67(2):189-194.
    [10] Tang W, Lu Y, Tian QY,et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice[J]. Science, 2011, 332(6028): 478-484.
    [11] Deng GM, Zheng LX,Lenardo M,et al. Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptors[J].Nat Med,2005,10(11):1066-1072.
    [12] Hwang JR, Huh JH, Lee Y,et al. Insulin-like growth factor-binding protein-5 (IGFBP-5) inhibits TNF-a-induced NF-κB activity by binding to TNFR1[J]. Biochem Biophys Res Commun, 2011,405(4): 545-551.
    [13] Mukai Y, Shibata H, Nakamura T,et al. Structure-function relationship of tumor necrosis factor (TNF) and its receptor interaction based on 3D structural analysis of a fully active TNFR1-selective TNF mutant[J].J Mol Biol, 2009, 385(4):1221-1229.
    [14] Takasaki W,KajinoY,KajinoK,et al.Structure-based design and characterization of exocyclic peptidomimetics that inhibit TNF-αbinding to its receptor[J]. Nat Biotechnol, 1997, 15:1266-1270.
    [15] Mukaro. Selective activation of tumour necrosis factor receptor-mediated intacellular signalling pathways[D].Adelaide: School of Paediatrics and Reproductive Health,2009.
    [16] Chidnos-Rojas CL,Steward MW,PartidosCD,et al.Apeptidomimetic antagonist of TNF-alpha-mediated cytotoxicity identified from a phage-displayed random peptide library[J]. J Immunol,1998,161(10):5621-5626.
    [17] 尹丙姣,黄丽霞,梁慧芳,等.TNFR1封闭肽-hIgGFc融合蛋白和TNFR1封闭肽对TNF-α介导的生物学效应的封闭作用[J].中国免疫学杂志,2008,24(9):776-780.
    [18] Liang H, Yin B, Zhang H,et al. Blockade of tumor necrosis factor (TNF) receptor type1-mediated TNF-α signaling protected wistarrats from diet-Induced obesity and insulin resistance[J]. Endocrinology, 2008, 149(6):2943-2951.
    [19] Roland E,Sabine M,Jens N,et al. A humanized tumor necrosis factor receptor 1 (TNFR1)-specific antagonistic antibody for selective inhibition of tumor necrosis factor (TNF)action[J].J Immunother,2008,31(3):225-234.
    [20] Carter PH, Scherle PA, Muckelbauer JK,et al. Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-a[J]. PNAS, 2001,98(21):11879-11884.
    [21] Murali R, Cheng X, Berezov A,et al. Disabling TNF receptor signaling by induced conformational perturbation of tryptophan-107[J]. PNAS,2005,102(31):10970-10975.
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  • 收稿日期:  2014-04-18
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肿瘤坏死因子受体选择性拮抗剂的研究进展

doi: 10.3969/j.issn.1006-0111.2015.05.003
    基金项目:  国家自然科学基金(30500093);国家科技部"重大新药创制"专项(2009ZX09103-690);上海市科委重点项目(04JC14002);军队"十一五"计划(06Q042);上海市高校优秀青年教师科研专项基金(ejd09011)

摘要: 肿瘤坏死因子(TNF)信号通路是很有价值的治疗靶标,抗TNF药物已成功治疗自身免疫和炎症疾病,但传统的抗TNF药物完全封闭TNF信号通路,导致影响自身的免疫调节和监视功能而增加感染、致癌的风险和产生新的自身免疫疾病。选择性抑制sTNF/TNFR1而保留mTNF/TNFR2传导的信号能减少副作用而不降低治疗效果。该文探讨了选择性抑制TNFR1介导的信号通路对治疗TNF相关疾病的意义,分析TNF识别并激活肿瘤坏死因子受体(TNFR)的作用机制,可能会为设计新药提供新的思路。

English Abstract

江海龙, 王宁远, 陆一鸣. 肿瘤坏死因子受体选择性拮抗剂的研究进展[J]. 药学实践与服务, 2015, 33(5): 392-395. doi: 10.3969/j.issn.1006-0111.2015.05.003
引用本文: 江海龙, 王宁远, 陆一鸣. 肿瘤坏死因子受体选择性拮抗剂的研究进展[J]. 药学实践与服务, 2015, 33(5): 392-395. doi: 10.3969/j.issn.1006-0111.2015.05.003
JIANG Hailong, WANG Ningyuan, LU Yiming. Research advance of selective inhibitor of tumornecrosis factor receptor[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(5): 392-395. doi: 10.3969/j.issn.1006-0111.2015.05.003
Citation: JIANG Hailong, WANG Ningyuan, LU Yiming. Research advance of selective inhibitor of tumornecrosis factor receptor[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(5): 392-395. doi: 10.3969/j.issn.1006-0111.2015.05.003
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