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！

全新药物设计方法与常用软件及其在抗癌药物设计中的应用

殷丽,  陈临溪

downloadPDF
文章导航 > 药学实践与服务  > 2014 >  32(1): 9-15,34
殷丽, 陈临溪. 全新药物设计方法与常用软件及其在抗癌药物设计中的应用[J]. 药学实践与服务, 2014, 32(1): 9-15,34. doi: 10.3969/j.issn.1006-0111.2014.01.003
引用本文: 殷丽, 陈临溪. 全新药物设计方法与常用软件及其在抗癌药物设计中的应用[J]. 药学实践与服务, 2014, 32(1): 9-15,34. doi: 10.3969/j.issn.1006-0111.2014.01.003
shu
YIN Li, CHEN Linxi. Applications of the common software and methods of denovo drug design in the antitumor drug design[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(1): 9-15,34. doi: 10.3969/j.issn.1006-0111.2014.01.003
Citation: YIN Li, CHEN Linxi. Applications of the common software and methods of denovo drug design in the antitumor drug design[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(1): 9-15,34. doi: 10.3969/j.issn.1006-0111.2014.01.003
shu

全新药物设计方法与常用软件及其在抗癌药物设计中的应用

doi: 10.3969/j.issn.1006-0111.2014.01.003

  • 南华大学药物药理研究所, 湖南 衡阳 421001

基金项目: 国家自然科学基金(81270420);教育部留学归国人员科研启动基金(20091590);湖南省高校创新平台开放基金(10K051);湖南省自然科学基金省市联合(衡阳)基金重点项目(12JJ8013);湖南省十二五重点学科资助.

Applications of the common software and methods of denovo drug design in the antitumor drug design

  • Institute of Pharmacy and Pharmacology, University of South China, Hunan Hengyang 421001, China

  • 摘要: 计算机辅助药物设计已普遍应用于药物研发过程,大大加快了药物开发的速度。特别是全新药物设计方法可以用于识别作用于特异性靶点的全新配体结构。全新药物设计常用软件有LUDI,LigBuilder,LeapFrog,SPROUT和SYNOPSIS等,常用方法有片段连接、片段生长、侧链替换和骨架跃迁等。全新药物设计方法在一些抗癌化合物,如纺锤体驱动蛋白抑制剂、血管内皮生长因子抑制剂、亲环蛋白A抑制剂和BRAF抑制剂等的发现方面,已经发挥了重要作用。综述全新药物设计方法与常用软件,并举例讨论其在新型抗癌药物领域中的应用。
    Abstract: Computer aided drug design had become part of the drug discovery process, greatly improved the speed of drug development compared with traditional drug finding methods. In particular, the de novo drug design method could be used to identify ligands with novel structure for a special target. Through computer simulation, researchers could find new ideas about how to change a compound to improve the drug properties or how to assemble some fragments to generate candidates which be drug-like, synthetically accessible and high affinity for a target. The common software of de novo design included LUDI, MCSS, LigBuilder, SPROUT, SYNOPSIS, BREED, LeapFrog and RACHEL, etc. The methods were fragments link and grow, side chain replacement, parent molecule evolve, template, scaffold hopping and so on. Discovery and development of cancer drugs had been revolutionized over the last decade. De novo drug design methods had already played a significant role in the discovery of some anticancer compounds such as kinesin spindle protein inhibitors, vascular endothelial growth factor inhibitors, cyclophilin A inhibitors, cell division cycle protein CDC25 inhibitors and BRAF inhibitors. The common software and methods of de novo drug design were summarized in this review and their applications in antitumor drug design were discussed.
  • [1] Hoelder S, Clarke PA, Workman P. Discovery of small molecule cancer drugs:successes, challenges and opportunities[J]. Mol Oncol, 2012, 6 (2):155-176.
    [2] Kalyaanamoorthy S, Phoebe Chen Y-P. Structure-based drug design to augment hit discovery[J]. Drug Discov Today, 2011, 16(17-18):831-839.
    [3] Kutchukian PS, Shakhnovich EI. De novo design:balancing novelty and confined chemical space[J]. Expert Opin Drug Discov, 2010. 5(8), 789-812.
    [4] Park H, Jeong Y, Hong S. Structure-based de novo design and biochemical evaluation of novel BRAF kinase inhibitors[J]. Bioorg Med Chem Lett, 2012, 22(2):1027-1030.
    [5] Schneider G, Fechner U. Computer-based de novo design of drug-like molecules[J]. Nat Rev Drug Discov 2005, 4 (8):694-663.
    [6] Lipinski,C, Hopkins A. Navigating chemical space for biology and medicine[J]. Nature, 2004,432(7019):855-861.
    [7] Platania CB, Salomone S, Leggio GM, et al. Homology modeling of dopamine d(2) and d(3) receptors:molecular dynamics refinement and docking evaluation[J]. PloS One, 2012, 7 (9):44316.
    [8] Keseru GM, Makara GM. Hit discovery and hit-to-lead approaches[J]. Drug Discov Today, 2006, 11(15-16), 741-748.
    [9] Bohm HJ. The computer program LUDI:a new method for de novo design of enzyme inhibitors[J]. J Comput Aided Mol Des, 1992, 6 (1):61-78.
    [10] Wang RX, Gao Y, Lai LH. LigBuilder:a multi-purpose progrom for structure-based drug design[J]. J Mol Model, 2000, 6 (7-8); 498-516.
    [11] Wang RX, Liu L, Lai LH, et al. SCORE:A new empirical method for estimating the binding affinity of a protein-ligand complex[J]. J Mol Model, 1998, 4 (12):370-394.
    [12] Yuan,YX, Pei JF, Lai LH. LigBuilder 2:a practical de novo drug design approach[J]. J Chem Inform Model, 2011, 51 (5):1083-1091.
    [13] Cramer RD. Design and preliminary results of LeapFrog, a second generation de novo drug discovery tool[J]. J Mol Graphics, 1993, 11(4); 271-272.
    [14] Ambure PS, Gangwal RP, Sanganwar AT. 3D-QSAR and molecular docking analysis of biphenyl amide derivatives as p38α mitogen-activated protein kinase inhibitors[J]. Mol Divers, 2012,16(2):377-388.
    [15] Makhija MT, Kasliwal RT, Kulkarni VM, et al. De novo design and synthesis of HIV-1 integrase inhibitors[J]. Bioorg Med Chem, 2004, 12(9):2317-2333.
    [16] Schinerider G, Neidhart W, Giller T, et al. Scaffold-Hopping by topological search:a contribution to virtual screening[J]. Angewandte Chemie (International Ed. in English), Angew Chem Int Ed Engl, 1999, 38(19):2894-2896.
    [17] Schneider G. De novo design-hopping against hope[EB/OL]. Drug Discovery Today:Technologies.(2012-06-20)[2013-01-02].
    [18] Wolber G. 3D pharmacophore elucidation and virtual screening[J]. Drug Discov Today, 2010, 7(4):203-204.
    [19] Lauri G, Bartlett PA. CAVEAT:a program to facilitate the design of organic molecules[J]. J Comput Aided Mol Des, 1994, 8(1):51-66.
    [20] Beno BR, Langley DR. MORPH:a new tool for ligand design[J]. J Chem Inform Model, 2010, 50(6):1159-1164.
    [21] Maass P, Schulz-Gasch T, Stahl M, et al. Recore:a fast and versatile method for scaffold hopping based on small molecule crystal structure conformations[J]. J Chem Inform Model, 2007,47(2):390-399.
    [22] Gillet VJ, Newell W, Mata P, et al. SPROUT:recent developments in the de novo design of molecules[J]. J Chem Inform Comput Sci, 1994, 34:207-217.
    [23] Vinkers HM, de Jonge MR, Daeyaert FF, et al. SYNOPSIS:SYNthesize and optimize system in silico[J]. J Med Chem, 2003, 46:2765-2773.
    [24] Pierce AC, Rao G, Bemis GW, et al. BREED generating novel inhibitors through hybridization of known ligands. Aplication to CDK2, p38and HIV protease[J]. J Med Chem, 2004, 47:2768-2775.
    [25] Marra E, Palombo F, Ciliberto G, et al. Intratumoral electro-transfer of small interfering RNA against kinesin spindle protein (KSP) slows down tumor progression[J]. J Cell Physiol, 2013,228(1),58-64.
    [26] Jiang,C, Yang L, Wu WT, et al. De novo design, synthesis and biological evaluation of 1,4-dihydroquinolin-4-ones and 1,2,3,4-tetrahydroquinazolin-4-ones as potent kinesin spindle protein (KSP) inhibitors[J]. Bioorg Med Chem, 2011,19 (18):5612-5627.
    [27] Kim LA, D'Amore PA. A brief history of anti-VEGF for the treatment of ocular angiogenesis[J]. Am J Pathol, 2012, 181(2):376-379.
    [28] Uno M, Ban HS, Nabeyama W, et al. De novo design and synthesis of N-benzylanilines as new candidates for VEGFR tyrosine kinase inhibitors[J]. Org Biomol Chem, 2008, 6 (6):979-981.
    [29] Albert H, Santos S, Battaqlia E, et al. Differential expression of CDC25 phosphatases splice variants in human breast cancer cells[J]. Clin Chem Lab Med, 2011, 49(10):1707-1714.
    [30] Park H, Bahn YJ, Ryu SE, Structure-based de novo design and biochemical evaluation of novel Cdc25 phosphatase inhibitors[J]. Bioorg Med Chem Lett, 2009, 19(15):4330-4334.
    [31] Zhou DJ, Mei Q, Li JT, et al, Cyclophilin A and viral infections[J]. Bioch Biophys Res Comm, 2012,424(4), 647-650.
    [32] Choi KJ, Piao YJ, Lim MJ, et al. Overexpressed cyclophilin A in cancer cells renders resistance to hypoxia-and cisplatin-induced cell death[J]. Cancer Res, 2007, 67(8):3654-3662.
    [33] Ni SS, Yuan YX, Huang J, et al. Discovering potent small molecule inhibitors of cyclophilin A using de novo drug design approach[J]. J Med Chem, 2009, 52(17):5295-5298.
    [34] Wong C, Chen S. The development,application and limitations of breast cancer cell lines to study tamoxifen and aromataes inhibitor resistance[J]. J Steroid Biochem Mol Biol, 2012, 131(3-5):83-92.
    [35] Gueto C, Torres J, Vivas-Reyes R. CoMFA, LeapFrog and blind docking studies on sulfonanilide derivatives acting as selective aromatase expression regulators[J]. Eur J Med Chem, 2009, 44(9):3445-3451.
    [36] Su B, Diaz-Cruz ES, Landini S, et al. Novel sulfonanilide analoguew suppress aromataes expression and activity in breast cancer cells independent of COX-2 inhibiton[J]. J Med Chem, 2006, 49(4):1413-1419.
    [37] Davies H, Bignell GR, Cox C, et al. Mutations of the B-raf gene in human cancer[J]. Nature, 2002, 417(6892), 949-954.
    [38] Gopalsamy A, Shi M, Hu Y, et al. B-raf kinase inhibitors:hit enrichment through scaffold hopping[J]. Bioorg Med Chem Lett, 2010, 20(8):2431-2434.
  • [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] 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
    [3] 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
    [4] 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
    [5] 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
    [6] 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
    [7] 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
    [8] 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
    [9] 凯丽比努尔·奥布力艾散, 李倩, 谢志, 贾文彦, 尹东锋.  星点设计-效应面法优化仑伐替尼混合胶束的制备工艺 . 药学实践与服务, 2024, 42(11): 495-502. doi: 10.12206/j.issn.2097-2024.202403019
    [10] 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
    [11] 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
  • 加载中
WeChat 点击查看大图
计量
  • 文章访问数:  3262
  • HTML全文浏览量:  281
  • PDF下载量:  508
  • 被引次数: 0
出版历程
  • 收稿日期:  2013-02-21
  • 修回日期:  2013-09-06

全新药物设计方法与常用软件及其在抗癌药物设计中的应用

doi: 10.3969/j.issn.1006-0111.2014.01.003
  • 南华大学药物药理研究所, 湖南 衡阳 421001
    • 基金项目:  国家自然科学基金(81270420);教育部留学归国人员科研启动基金(20091590);湖南省高校创新平台开放基金(10K051);湖南省自然科学基金省市联合(衡阳)基金重点项目(12JJ8013);湖南省十二五重点学科资助.
  • 收稿日期: 2013-02-21
  • 修回日期: 2013-09-06

摘要: 计算机辅助药物设计已普遍应用于药物研发过程,大大加快了药物开发的速度。特别是全新药物设计方法可以用于识别作用于特异性靶点的全新配体结构。全新药物设计常用软件有LUDI,LigBuilder,LeapFrog,SPROUT和SYNOPSIS等,常用方法有片段连接、片段生长、侧链替换和骨架跃迁等。全新药物设计方法在一些抗癌化合物,如纺锤体驱动蛋白抑制剂、血管内皮生长因子抑制剂、亲环蛋白A抑制剂和BRAF抑制剂等的发现方面,已经发挥了重要作用。综述全新药物设计方法与常用软件,并举例讨论其在新型抗癌药物领域中的应用。

English Abstract

殷丽, 陈临溪. 全新药物设计方法与常用软件及其在抗癌药物设计中的应用[J]. 药学实践与服务, 2014, 32(1): 9-15,34. doi: 10.3969/j.issn.1006-0111.2014.01.003
引用本文: 殷丽, 陈临溪. 全新药物设计方法与常用软件及其在抗癌药物设计中的应用[J]. 药学实践与服务, 2014, 32(1): 9-15,34. doi: 10.3969/j.issn.1006-0111.2014.01.003
shu
YIN Li, CHEN Linxi. Applications of the common software and methods of denovo drug design in the antitumor drug design[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(1): 9-15,34. doi: 10.3969/j.issn.1006-0111.2014.01.003
Citation: YIN Li, CHEN Linxi. Applications of the common software and methods of denovo drug design in the antitumor drug design[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(1): 9-15,34. doi: 10.3969/j.issn.1006-0111.2014.01.003
shu

    全文HTML

参考文献 (38)

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