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] 李锐, 张倩倩, 王瑞冬, 高小峰.  国家集中带量采购政策下样本医院良性前列腺增生治疗药物使用情况分析 . 药学实践与服务, 2025, 43(2): 1-6. doi: 10.12206/j.issn.2097-2024.202408031
    [2] 毛智毅, 王筱燕, 陈晓颖, 汤逸斐.  度拉糖肽联合二甲双胍对肥胖型2型糖尿病患者机体代谢、体脂成分及血清脂肪因子的影响 . 药学实践与服务, 2024, 42(7): 305-309. doi: 10.12206/j.issn.2097-2024.202305032
    [3] 陈炳辰, 佟达丰, 万苗, 闫飞虎, 姚建忠.  UPLC-MS/MS法测定小鼠血浆中紫杉醇脂肪酸酯前药及其药代动力学研究 . 药学实践与服务, 2024, 42(8): 341-345. doi: 10.12206/j.issn.2097-2024.202404082
    [4] 郭灵怡, 刘艳超, 高路, 刘瑞瑶, 吕权真, 俞媛.  醋酸卡泊芬净单硬脂酸甘油酯纳米粒抗白色念珠菌感染的增效作用研究 . 药学实践与服务, 2024, 42(): 1-8. doi: 10.12206/j.issn.2097-2024.202310043
    [5] 戴菲菲, 傅翔, 陈琼年, 俞苏纯.  上海某二级医院革兰阴性菌流行特征的回顾性分析 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202305005
    [6] 陈炳辰, 王思真, 郭贝贝, 杨峰.  紫杉醇棕榈酸酯的合成及其脂质体的制备与处方研究 . 药学实践与服务, 2024, 42(9): 379-384, 410. doi: 10.12206/j.issn.2097-2024.202404062
    [7] 崔亚玲, 吴琼, 马良煜, 胡北, 姚东, 许子华.  肝素钠肌醇烟酸酯乳膏中肌醇烟酸酯皮肤药动学研究 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404006
    [8] 宋雨桐, 夏德润, 顾珩, 唐少文, 易洪刚, 沃红梅.  帕博利珠单抗与铂类化疗方案在晚期非小细胞肺癌一线治疗中的药物经济学评价 . 药学实践与服务, 2024, 42(8): 334-340. doi: 10.12206/j.issn.2097-2024.202303023
    [9] 孙丹倪, 黄勇, 张嘉宝, 王培.  代谢相关脂肪性肝病的无创诊断与药物治疗 . 药学实践与服务, 2024, 42(10): 411-418. doi: 10.12206/j.issn.2097-2024.202403049
    [10] 陈怡君, 王卓, 何苗, 张宇, 田泾.  泌尿系统碎石术抗菌药物预防使用合理管控实践 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202402034
    [11] 张岩, 李炎君, 刘家荟, 邓娇, 原苑, 张敬一.  药物性肝损伤不良反应分析 . 药学实践与服务, 2024, 42(): 1-5. doi: 10.12206/j.issn.2097-2024.202404034
    [12] 张元林, 宋凯, 孙蕊, 舒飞, 舒丽芯, 杨樟卫.  基于真实世界数据的药物利用研究综述 . 药学实践与服务, 2024, 42(6): 238-243. doi: 10.12206/j.issn.2097-2024.202312010
    [13] 刘丽艳, 余小翠, 孙传铎.  纳武利尤单抗治疗非小细胞肺癌有效性及安全性的Meta分析 . 药学实践与服务, 2024, 42(10): 451-456. doi: 10.12206/j.issn.2097-2024.202310044
    [14] 张艺昕, 关欣怡, 王博宁, 闻俊, 洪战英.  二氢吡啶类钙离子拮抗药物手性分析及其立体选择性药动学研究进展 . 药学实践与服务, 2024, 42(8): 319-324. doi: 10.12206/j.issn.2097-2024.202308062
    [15] 夏哲炜, 曾垣烨, 朱海菲, 李育, 陈啸飞.  核磁共振磷谱法测定磷酸氢钙咀嚼片中药物含量 . 药学实践与服务, 2024, 42(9): 399-401, 406. doi: 10.12206/j.issn.2097-2024.202404063
    [16] 赖立勇, 夏天爽, 徐圣焱, 蒋益萍, 岳小强, 辛海量.  中药青蒿抗氧化活性的谱效关系研究 . 药学实践与服务, 2024, 42(5): 203-210, 216. doi: 10.12206/j.issn.2097-2024.202211012
  • 加载中
WeChat 点击查看大图
计量
  • 文章访问数:  3558
  • HTML全文浏览量:  397
  • PDF下载量:  881
  • 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: [email protected]

    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