Lagorce David, Sperandio Olivier, Baell Jonathan B, Miteva Maria A, Villoutreix Bruno O
Université Paris Diderot, Sorbonne Paris Cité, Molécules Thérapeutiques In Silico, Paris 75013, France Inserm U973, Molécules Thérapeutiques In Silico, Paris 75013, France.
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Nucleic Acids Res. 2015 Jul 1;43(W1):W200-7. doi: 10.1093/nar/gkv353. Epub 2015 Apr 16.
Drug attrition late in preclinical or clinical development is a serious economic problem in the field of drug discovery. These problems can be linked, in part, to the quality of the compound collections used during the hit generation stage and to the selection of compounds undergoing optimization. Here, we present FAF-Drugs3, a web server that can be used for drug discovery and chemical biology projects to help in preparing compound libraries and to assist decision-making during the hit selection/lead optimization phase. Since it was first described in 2006, FAF-Drugs has been significantly modified. The tool now applies an enhanced structure curation procedure, can filter or analyze molecules with user-defined or eight predefined physicochemical filters as well as with several simple ADMET (absorption, distribution, metabolism, excretion and toxicity) rules. In addition, compounds can be filtered using an updated list of 154 hand-curated structural alerts while Pan Assay Interference compounds (PAINS) and other, generally unwanted groups are also investigated. FAF-Drugs3 offers access to user-friendly html result pages and the possibility to download all computed data. The server requires as input an SDF file of the compounds; it is open to all users and can be accessed without registration at http://fafdrugs3.mti.univ-paris-diderot.fr.
临床前或临床开发后期的药物淘汰是药物研发领域一个严重的经济问题。这些问题部分可归因于在活性化合物发现阶段所使用的化合物库的质量，以及正在进行优化的化合物的选择。在此，我们介绍FAF-Drugs3，这是一个网络服务器，可用于药物研发和化学生物学项目，以帮助制备化合物库，并在活性化合物筛选/先导化合物优化阶段协助决策。自2006年首次被描述以来，FAF-Drugs已得到显著改进。该工具现在应用了增强的结构整理程序，可以使用用户定义的或八个预定义的物理化学过滤器以及几个简单的ADMET（吸收、分布、代谢、排泄和毒性）规则对分子进行过滤或分析。此外，可以使用154个手动整理的结构警示的更新列表对化合物进行过滤，同时还会研究泛测定干扰化合物（PAINS）和其他通常不需要的基团。FAF-Drugs3提供用户友好的html结果页面，并允许下载所有计算数据。该服务器需要输入化合物的SDF文件；它对所有用户开放，无需注册即可通过http://fafdrugs3.mti.univ-paris-diderot.fr访问。
