计算机药物设计:一种彻底改变药物发现过程的方法

Abdul Wadood, N. Ahmed, L. Shah, Ashfaq Ahmad, Hammad Hassan, Sulaiman Shams
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It has kept on comparatively unaffected since 1980 with a present time period of 9-13 years.1,4 According to pharmaceutical research and manufacturers the estimated cost of the complete drug discovery process is about US$880 million and takes up to 14 years from initial research stage to the successful marketing of an new drug in 2001.4 The recent figures of DiMasi at the Tufts Centre for Study of Drug Development (CSDD) is about US$802 million spread over 12 years, which was reported in 2003,4 while the Boston Consulting Group estimates the cost as $880 million over 15 years. 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引用次数: 83

摘要

药物的发现和开发是一个激烈的、漫长的、跨学科的冒险。最近,在计算机辅助药物设计中使用硅化学和分子模型的趋势已经获得了显著的势头。Insilico药物设计技术应用于纳米技术、分子生物学、生物化学等领域。计算机药物设计的主要优点是在药物研究和开发方面具有成本效益。有广泛的软件用于硅药物设计,网格计算,基于窗口的通用PBPK/PD建模软件,PKUDDS用于基于结构的药物设计,api, JAVA, Perl和Python,硅药物设计以及包括软件库在内的软件。在药物设计、可视化、同源性、分子动力学、能量最小化、分子对接和QSAR等方面有不同的技术应用。从临床前发现阶段到后期临床开发阶段,计算机药物设计可以在药物开发的各个阶段发挥重要作用。它在药物开发中的利用有助于只选择一个有效的先导分子,从而可能阻止晚期临床失败;这样就可以大大降低成本。这篇文章给出了一个洞察所有方面的硅药物设计;它的潜力、动力、发展现状和未来前景。结论计算机方法在新药的靶点鉴定和药物预测中具有重要的应用价值。药物的发现和开发是一个非常复杂、耗时的过程,导致不同药物失败的因素有很多,如缺乏有效性、副作用、药代动力学差和市场原因。这一进程的开支在过去34年里不祥地扩大了。药品制造商协会收到的行业平均报告显示,药物开发的支出已从1962年的400万美元增加到1996年的3.5亿美元以上。从1960年到1980年,一种药物从第一次合成到上市的改进时间几乎翻了一番。自1980年以来,它一直保持相对不受影响,目前的时间周期为9-13年。1 4根据药品研究与制造商完整的药物发现过程的估计成本大约是8.8亿美元,占到14年从最初研究阶段的成功的营销新药物在2001.4的最近的数据在塔夫茨DiMasi药物开发研究中心(CSDD)约8.02亿美元在12年,于2003年被报道,4日,波士顿咨询集团(Boston Consulting Group)估计,成本8.8亿美元超过15年。目前,药物研发过程所涉及的费用从8亿美元到18亿美元不等。计算机辅助药物设计中心的成立是为了支持生物学、生物物理学、结构生物学和计算科学家等不同领域的科学家进行联合研究CADDC申请的主要目标是启动这些伙伴关系,从而导致实施研究项目,以发现有可能转化为新治疗剂的新化合物。计算机药物设计是一个基础研究与实践相互结合、相互启发的广阔领域,QSAR/QSPR、基于结构的设计、组合文库设计、化学信息学、生物信息学等7种现代技术以及越来越多的生物和化学数据库被应用于该领域。此外,大量可用的工具为设计具有首选特异性的配体和抑制剂提供了非常成熟的基础本综述的目的是讨论芯片药物设计的过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In-silico drug design: An approach which revolutionarised the drug discovery process
Introduction Drug discovery and development is an intense, lengthy and an interdisciplinary venture. Recently, a trend towards the use of in-silico chemistry and molecular modelling for computer-aided drug design has gained significant momentum. Insilico drug design skills are used in nanotechnology, molecular biology, biochemistry etc. The main benefit of the in-silico drug design is cost effective in research and development of drugs. There are wide ranges of software that are used in in-silico drug design, Grid computing, window based general PBPK/PD modelling software, PKUDDS for structure based drug design, APIS, JAVA, Perl and Python, in-silico drug design as well as software including software libraries. There are different techniques used in in-silico drug design visualization, homology, molecular dynamic, energy minimization molecular docking and QSAR etc. In-silico drug design can take part considerably in all stages of drug development from the preclinical discovery stage to late stage clinical development. Its exploitation in drug development helps in the selection of only a potent lead molecule and may thus thwart the late stage clinical failures; thereby a major diminution in cost can be achieved. This article gives an insight into all the aspects of in-silico drug design; its potential, drivers, current development and the future prospects. Conclusion In-silico methods have been of great importance in target identification and in prediction of novel drugs. Introduction Drug discovery and development is a very complicated, time consuming process and there are many factors responsible for the failure of different drugs such as lack of effectiveness, side effects, poor pharmacokinetics, and marketable reasons. The expenditure of this process has amplified ominously during the past thirty-four years. The Pharmaceutical Manufacturer’s Association received the industry average reports which have shown that the expenditure of drug development has enlarged from $4 million in 1962 to over $350 million in 1996. The improvement time of a drug from the first synthesis to its foreword in the market, has almost multiplied between 1960 and 1980. It has kept on comparatively unaffected since 1980 with a present time period of 9-13 years.1,4 According to pharmaceutical research and manufacturers the estimated cost of the complete drug discovery process is about US$880 million and takes up to 14 years from initial research stage to the successful marketing of an new drug in 2001.4 The recent figures of DiMasi at the Tufts Centre for Study of Drug Development (CSDD) is about US$802 million spread over 12 years, which was reported in 2003,4 while the Boston Consulting Group estimates the cost as $880 million over 15 years. At present the cost involved in the drug discovery process ranges f rom $800 million to $1.8 billion,5 The establishment of the Computer-Aided Drug Design (CADD) Centre was to endorse joint research among the scientists of various fields like biology, biophysics, structural biology and computational scientists.6 The main objective of CADDC entries is to start these partnerships that lead to the implementation of research projects to discover new compounds with the potential to be transformed into new therapeutic agents. The in-silico drug design is a vast field in which the different sides of basic research and practice are combined and inspire each other,7 modern techniques such as QSAR/QSPR, structure-based design, combinatorial library design, cheminformatics, bioinformatics and the increasing number of biological and chemical databases are used in the field. Furthermore, large numbers of the available tools provide a much developed basis for the design of ligands and inhibitors with preferred specificity.8 The aim of this review was to discuss the process of In-silico drug design.
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