留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码
x 关闭 永久关闭

应中央军委要求，2022年9月起，《药学实践杂志》将更名为《药学实践与服务》，双月刊，正文96页；2023年1月起，拟出版月刊，正文64页，数据库收录情况与原《药学实践杂志》相同。欢迎作者踊跃投稿！

酪氨酸-DNA磷酸二酯酶抑制剂的研究进展

黄亚辉,  董国强,  张万年,  盛春泉

downloadPDF
文章导航 > 药学实践与服务  > 2015 >  33(4): 298-302
黄亚辉, 董国强, 张万年, 盛春泉. 酪氨酸-DNA磷酸二酯酶抑制剂的研究进展[J]. 药学实践与服务, 2015, 33(4): 298-302. doi: 10.3969/j.issn.1006-0111.2015.04.003
引用本文: 黄亚辉, 董国强, 张万年, 盛春泉. 酪氨酸-DNA磷酸二酯酶抑制剂的研究进展[J]. 药学实践与服务, 2015, 33(4): 298-302. doi: 10.3969/j.issn.1006-0111.2015.04.003
shu
HUANG Yahui, DONG Guoqiang, ZHANG Wannian, SHENG Chunquan. Recent advances of tyrosyl-DNA phosdiesterase Ⅰ (TdpⅠ) inhibitors[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 298-302. doi: 10.3969/j.issn.1006-0111.2015.04.003
Citation: HUANG Yahui, DONG Guoqiang, ZHANG Wannian, SHENG Chunquan. Recent advances of tyrosyl-DNA phosdiesterase Ⅰ (TdpⅠ) inhibitors[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 298-302. doi: 10.3969/j.issn.1006-0111.2015.04.003
shu

酪氨酸-DNA磷酸二酯酶抑制剂的研究进展

doi: 10.3969/j.issn.1006-0111.2015.04.003

  • 第二军医大学药学院, 上海 200433

基金项目: 国家优秀青年科学基金(No.81222044)

Recent advances of tyrosyl-DNA phosdiesterase Ⅰ (TdpⅠ) inhibitors

  • School of Pharmacy, Second Military Medical University, Shanghai 200433, China

  • 摘要: 酪氨酸-DNA磷酸二酯酶Ⅰ(tyrosyl-DNA-phosphodiesterase Ⅰ,TdpⅠ)是一个具有催化3'磷酸酪氨酸键水解活性的蛋白质,该键在拓扑异构酶Ⅰ(topoisomerase Ⅰ, TopⅠ)与DNA相互作用时就会形成。由于TdpⅠ具有修复TopⅠ-DNA复合物、抵消TopⅠ抑制剂作用的功能,因而与TopⅠ共同被认作是潜在治疗靶标。TdpⅠ抑制剂不仅与TopⅠ抑制剂(喜树碱类)起到协同作用,还能增强博来霉素、TopⅡ抑制剂(依托泊苷、多柔比星)以及DNA烷化剂作用。综述目前报道的TdpⅠ抑制剂研究进展,重点介绍其作用机制、生物活性及构效关系。
    Abstract: Tyrosyl-DNA phosphodiesterase Ⅰ (TdpⅠ) is a recently discovered proteinthat catalyzes the hydrolysis of 3'-phosphotyrosyl bonds. Such linkages form in vivo during the interaction of DNA and topoisomerase Ⅰ (TopⅠ). TdpⅠ has been regarded as a potential therapeutic co-target of TopⅠ because it has the functions of repairing TopⅠ compound and counteracting the effects of TopⅠ inhibitors. TdpⅠ inhibitors can not only synergizing with TopⅠ-targeting drugs (camptothecins), but also strength the function of bleomycin, topoisomerase Ⅱ (TopⅡ) inhibitors (etoposide, doxorubicin) and DNA alkylating agents. We summarized the researching advance of TdpⅠ inhibitors and focused on the introduction of the mechanism, bioactivity and structure-activity relationship.
  • [1] Wang JC. DNA topoisomerases[J]. Annu Rev Biochem, 1996, 65:635-692.
    [2] Pommier Y. Topoisomerase I inhibitors: camptothecins and beyond[J]. Nat Rev Cancer, 2006, 6(10):789-802.
    [3] Champoux JJ. DNA topoisomerases: structure, function, and mechanism[J]. Annu Rev Biochem, 2001, 70:369-413.
    [4] Pourquier P, Pommier Y. Topoisomerase I-mediated DNA damage[J]. Adv Cancer Res, 2001, 80:189-216.
    [5] Pourquier P, Pilon AA, Kohlhagen G, et al. Trapping of mammalian topoisomerase I and recombinations induced by damaged DNA containing nicks or gaps. Importance of DNA end phosphorylation and camptothecin effects[J]. J Biol Chem, 1997, 272(42):26441-26447.
    [6] Yang SW, Burgin AB,, Huizenga BN Jr, et al. A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases[J]. Proc Natl Acad Sci U S A, 1996, 93(21):11534-11539.
    [7] Pouliot JJ, Yao KC, Robertson CA, et al. Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes[J]. Science, 1999, 286(5439):552-555.
    [8] El-Khamisy SF, Saifi GM, Weinfeld M, et al. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1[J]. Nature, 2005, 434(7029):108-113.
    [9] Plo I, Liao ZY, Barcelo JM, et al. Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions[J]. DNA Repair (Amst), 2003, 2(10):1087-1100.
    [10] Whitehouse CJ, Taylor RM, Thistlethwaite A, et al. XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair[J]. Cell, 2001, 104(1):107-117.
    [11] Pommier Y, Redon C, Rao VA, et al. Repair of and checkpoint response to topoisomerase I-mediated DNA damage[J]. Mutat Res, 2003, 532(1-2):173-203.
    [12] Takashima H, Boerkoel CF, John J, et al. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy[J]. Nat Genet, 2002, 32(2):267-272.
    [13] El-Khamisy SF, Katyal S, Patel P, et al. Synergistic decrease of DNA single-strand break repair rates in mouse neural cells lacking both Tdp1 and aprataxin[J]. DNA Repair (Amst), 2009, 8(6):760-766.
    [14] Das BB, Antony S, Gupta S, et al. Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK[J]. EMBO J, 2009, 28(23):3667-3680.
    [15] Katyal S, el-Khamisy SF, Russell HR, et al. TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo[J]. EMBO J, 2007, 26(22):4720-4731.
    [16] Hirano R, Interthal H, Huang C, et al. Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation?[J]. EMBO J, 2007, 26(22):4732-4743.
    [17] Barthelmes HU, Habermeyer M, Christensen MO, et al. TDP1 overexpression in human cells counteracts DNA damage mediated by topoisomerases I and II[J]. J Biol Chem, 2004, 279(53):55618-55625.
    [18] Nivens MC, Felder T, Galloway AH, et al. Engineered resistance to camptothecin and antifolates by retroviral coexpression of tyrosyl DNA phosphodiesterase-I and thymidylate synthase[J]. Cancer Chemother Pharmacol, 2004, 53(2):107-115.
    [19] Pommier Y, Barcelo JM, Rao VA, et al. Repair of topoisomerase I-mediated DNA damage[J]. Prog Nucleic Acid Res Mol Biol, 2006, 81:179-229.
    [20] Dexheimer TS, Antony S, Marchand C, et al. Tyrosyl-DNA phosphodiesterase as a target for anticancer therapy[J]. Anticancer Agents Med Chem, 2008, 8(4):381-389.
    [21] Liao Z, Thibaut L, Jobson A, et al. Inhibition of human tyrosyl-DNA phosphodiesterase by aminoglycoside antibiotics and ribosome inhibitors[J]. Mol Pharmacol, 2006, 70(1):366-372.
    [22] Antony S, Marchand C, Stephen AG, et al. Novel high-throughput electrochemiluminescent assay for identification of human tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors and characterization of furamidine (NSC 305831) as an inhibitor of Tdp1[J]. Nucleic Acids Res, 2007, 35(13):4474-4484.
    [23] Marchand C, Lea WA, Jadhav A, et al. Identification of phosphotyrosine mimetic inhibitors of human tyrosyl-DNA phosphodiesterase I by a novel AlphaScreen high-throughput assay[J]. Mol Cancer Ther, 2009, 8(1):240-248.
    [24] Dexheimer TS, Gediya LK, Stephen AG, et al. 4-Pregnen-21-ol-3,20-dione-21-(4-bromobenzenesulfonate) (NSC 88915) and related novel steroid derivatives as tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors[J]. J Med Chem, 2009, 52(22):7122-7131.
    [25] Weidlich IE, Dexheimer T, Marchand C, et al. Inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1) developed by virtual screening using ligand-based pharmacophores[J]. Bioorg Med Chem, 2010, 18(1):182-189.
    [26] Takagi M, Ueda JY, Hwang JH, et al. Tyrosyl-DNA phosphodiesterase 1 inhibitor from an anamorphic fungus[J]. J Nat Prod, 2012, 75(4):764-767.
    [27] Nguyen TX, Morrell A, Conda-Sheridan M, et al. Synthesis and biological evaluation of the first dual tyrosyl-DNA phosphodiesterase I (Tdp1)-topoisomerase I (Top1) inhibitors[J]. J Med Chem, 2012, 55(9):4457-4478.
    [28] Sirivolu VR, Vernekar SK, Marchand C, et al. 5-Arylidenethioxothiazolidinones as inhibitors of tyrosyl-DNA phosphodiesterase I[J]. J Med Chem, 2012, 55(20):8671-8684.
  • [1] 叶腾飞, 程涛, 宋平, 计伟莉, 卞晓岚.  8-羟基喹啉衍生物作为潜在的艰难梭菌抗生素的设计、合成和活性评价 . 药学实践与服务, 2023, 41(12): 737-740. doi: 10.12206/j.issn.2097-2024.202303021
    [2] 王冬博, 聂晶, 武慧娜, 孙磊, 刘丽慧, 吴记勇.  铂类抗肿瘤药物耐药机制的研究进展和应对策略 . 药学实践与服务, 2022, 40(4): 302-308. doi: 10.12206/j.issn.1006-0111.202204046
    [3] 丁德英, 刘伟, 吕狄亚.  中药保健品中非法添加磷酸二酯酶-5抑制剂检测方法的研究进展 . 药学实践与服务, 2019, 37(2): 103-108. doi: 10.3969/j.issn.1006-0111.2019.02.002
    [4] 李晏, 周莉芬, 张斌.  某院抗肿瘤药物临床应用调查分析 . 药学实践与服务, 2016, 34(1): 86-89. doi: 10.3969/j.issn.1006-0111.2016.01.023
    [5] 蒋琰, 盛春泉, 董国强.  拓扑异构酶Ⅰ和Ⅱ双重抑制剂的研究进展 . 药学实践与服务, 2015, 33(4): 303-308,379. doi: 10.3969/j.issn.1006-0111.2015.04.004
    [6] 金鑫, 宋霞, 曹永兵, 姜远英, 孙青龑.  小檗碱的结构改造及其药理活性的研究进展 . 药学实践与服务, 2014, 32(3): 171-175. doi: 10.3969/j.issn.1006-0111.2014.03.003
    [7] 张涛, 王甜甜, 张一凯, 牛春娟, 李令振, 李科.  2-(4-三氟甲基苯基)-4-乙基-呋喃-3-酰胺衍生物的设计、合成及其抗肿瘤活性研究 . 药学实践与服务, 2014, 32(2): 98-101,120. doi: 10.3969/j.issn.1006-0111.2014.02.006
    [8] 武善超, 盛春泉, 张万年.  来源于天然产物的抗肿瘤先导结构研究进展 . 药学实践与服务, 2014, 32(5): 337-341,371. doi: 10.3969/j.issn.1006-0111.2014.05.005
    [9] 陈焕, 耿冬平, 李科.  N-取代苯基-2-(4-取代苯基)环丙烷-1-甲酸乙酯-1-酰胺的设计、合成及抗肿瘤活性 . 药学实践与服务, 2012, 30(6): 422-426,461. doi: 10.3969/j.issn.1006-0111.2012.06.007
    [10] 陈婷, 鲁莹.  载抗肿瘤药物纳米靶向给药系统的研究进展 . 药学实践与服务, 2011, 29(3): 176-178,196.
    [11] 廖俊, 刘超美.  依布硒啉及衍生物的药理作用和构效关系研究进展 . 药学实践与服务, 2010, 28(2): 84-87,104.
    [12] 王甜甜, 吕志良, 李科.  人免疫缺陷病毒整合酶抑制剂研究进展 . 药学实践与服务, 2009, 27(1): 24-30.
    [13] 王燕琼, 姜华, 陈敏玲, 李岚, 张春, 蒋樾廉.  几种常用抗肿瘤药物再配制后稳定性概况 . 药学实践与服务, 2007, (6): 401-403.
    [14] 董环文, 刘超美, 何秋琴, 赵荔华.  斑蝥素及其衍生物的抗肿瘤构效关系研究进展 . 药学实践与服务, 2007, (5): 276-280.
    [15] 丁力, 丁家崇, 郭葆玉.  抗肿瘤药物新靶点半胱天冬酶-10 . 药学实践与服务, 2006, (2): 76-79.
    [16] 王莉清, 陈志龙, 张招贵, 王建国.  血管紧张素Ⅱ受体拮抗剂替米沙坦研究进展 . 药学实践与服务, 2003, (1): 32-35.
    [17] 罗琼, 何晖, 潘菡清.  抗肿瘤药物在驻济南部队医院的用药分析 . 药学实践与服务, 2002, (1): 32-33.
    [18] 潘涛, 赵庆杰, 吕小伟, 潘亚菊, 吴秋业.  磷酸二酯酶5抑制剂的研究进展 . 药学实践与服务, 2002, (6): 365-370.
    [19] 李健和, 徐雯, 龙小华, 曾晓丹.  抗肿瘤药在输液中的稳定性及与其它药物的配伍变化 . 药学实践与服务, 1998, (6): 348-353.
    [20] 丁惠萍, 黄平.  抗肿瘤药物的药代动力学及血浓度测定 . 药学实践与服务, 1996, (1): 37-40.
  • 加载中
WeChat 点击查看大图
计量
  • 文章访问数:  2661
  • HTML全文浏览量:  254
  • PDF下载量:  872
  • 被引次数: 0
出版历程
  • 收稿日期:  2014-07-14
  • 修回日期:  2014-10-27

酪氨酸-DNA磷酸二酯酶抑制剂的研究进展

doi: 10.3969/j.issn.1006-0111.2015.04.003
  • 第二军医大学药学院, 上海 200433
    • 基金项目:  国家优秀青年科学基金(No.81222044)
  • 收稿日期: 2014-07-14
  • 修回日期: 2014-10-27

摘要: 酪氨酸-DNA磷酸二酯酶Ⅰ(tyrosyl-DNA-phosphodiesterase Ⅰ,TdpⅠ)是一个具有催化3'磷酸酪氨酸键水解活性的蛋白质,该键在拓扑异构酶Ⅰ(topoisomerase Ⅰ, TopⅠ)与DNA相互作用时就会形成。由于TdpⅠ具有修复TopⅠ-DNA复合物、抵消TopⅠ抑制剂作用的功能,因而与TopⅠ共同被认作是潜在治疗靶标。TdpⅠ抑制剂不仅与TopⅠ抑制剂(喜树碱类)起到协同作用,还能增强博来霉素、TopⅡ抑制剂(依托泊苷、多柔比星)以及DNA烷化剂作用。综述目前报道的TdpⅠ抑制剂研究进展,重点介绍其作用机制、生物活性及构效关系。

English Abstract

黄亚辉, 董国强, 张万年, 盛春泉. 酪氨酸-DNA磷酸二酯酶抑制剂的研究进展[J]. 药学实践与服务, 2015, 33(4): 298-302. doi: 10.3969/j.issn.1006-0111.2015.04.003
引用本文: 黄亚辉, 董国强, 张万年, 盛春泉. 酪氨酸-DNA磷酸二酯酶抑制剂的研究进展[J]. 药学实践与服务, 2015, 33(4): 298-302. doi: 10.3969/j.issn.1006-0111.2015.04.003
shu
HUANG Yahui, DONG Guoqiang, ZHANG Wannian, SHENG Chunquan. Recent advances of tyrosyl-DNA phosdiesterase Ⅰ (TdpⅠ) inhibitors[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 298-302. doi: 10.3969/j.issn.1006-0111.2015.04.003
Citation: HUANG Yahui, DONG Guoqiang, ZHANG Wannian, SHENG Chunquan. Recent advances of tyrosyl-DNA phosdiesterase Ⅰ (TdpⅠ) inhibitors[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(4): 298-302. doi: 10.3969/j.issn.1006-0111.2015.04.003
shu

    全文HTML

参考文献 (28)

目录

    /

    返回文章
    返回

    版权所有：《药学实践与服务》编辑委员会

    主管、主办: 中国人民解放军海军军医大学地址: 上海市杨浦区国和路325号邮政编码: 200433

    电话: （021）81871324,81871397 E-mail: yxsjzzs@163.com

    网站备案号 沪ICP备05003363号-1

    本系统由 北京仁和汇智信息技术有限公司 开发    百度统计