摘要
背景:目前抗癌治疗的许多障碍促使科学家发现新的药物。随着新靶标和策略以及近期生物和生物技术进步的不断增长,许多抗癌药物如单克隆抗体,小分子酪氨酸激酶抑制剂和表观遗传药物已进入临床试验阶段。 目标:本综述有助于理解抑制剂对细胞生长,增殖,存活,血管生成以及蛋白酶体,热休克蛋白和表观遗传学等最新靶点发展的基本原理。 方法:最近的基于靶向的抗癌药物开发方法的突出之处在于从经批准的药物中提供了一些例子。讨论了许多因素,如代谢变化,缺氧,癌症前体和抗癌细胞及其对耐药机制的影响。解释了高级计算技术对鉴定癌症靶点和设计更多选择性抑制剂的影响。 结果:已经解释了近期技术的贡献,例如网络分析,确切的作用模式和计算方法,特别是模拟生物分子过程以阐明目标,机制作用和抗癌药物缺乏效力的原因。讨论了几种机制与分子设计策略之间的关系。 结论:本综述概述了抗癌药物的重要目标和设计策略,以及这些方法的优缺点和临床研究中目前使用的一些抗癌目标的评估.
关键词: 癌症,表观遗传,激酶,血管生成,抗癌剂,主要靶点。
Current Medicinal Chemistry
Title:Overview on Anticancer Drug Design and Development
Volume: 25 Issue: 15
关键词: 癌症,表观遗传,激酶,血管生成,抗癌剂,主要靶点。
摘要: Background: Many impediments of current anti-cancer therapies have urged scientists to discover new agents. As a result of growing spectrums of new targets and strategies and recent biological and biotechnological progresses, many anti-cancer agents such as monoclonal antibodies, small molecule tyrosine kinase inhibitors and epigenetic drugs have been reached to clinical trials.
Objectives: This review helps to understand the rationale for the development of inhibitors against major targets such as cell growth, proliferation, survival, angiogenesis and recent targets such as proteasome, heat shock proteins, and epigenetics.
Methods: Recent approaches of the target-based anti-cancer drug developments were highlighted to giving some examples from approved agents. Many factors, such as metabolic change, hypoxia, cancer precursors and cancer resistant cells, and their effect on drug resistance mechanisms were discussed. The impacts of advanced computational techniques to identify targets of cancer and designing more selective inhibitors were explained.
Results: Contributions of recent techniques such as a network analysis, the precise modes of action and computational methodologies especially simulation of bio-molecular processes to clarify targets, mechanism actions and reasons of lack of efficacy of anti-cancer drugs have been explained. The relationship between the several mechanisms and molecular design strategies has been discussed.
Conclusion: This review provides an overview of important targets and design strategies of anti-cancer drugs, advantages and disadvantages of these methods and evaluation of some currently used anticancer targets in clinical studies.
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Cite this article as:
Overview on Anticancer Drug Design and Development, Current Medicinal Chemistry 2018; 25 (15) . https://dx.doi.org/10.2174/0929867325666171129215610
DOI https://dx.doi.org/10.2174/0929867325666171129215610 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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