eADMET GmbH, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.
J Chem Inf Model. 2012 Aug 27;52(8):2310-6. doi: 10.1021/ci300245q. Epub 2012 Aug 10.
The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at http://ochem.eu/alerts, and it is constantly growing.
本文提出了一个基于网络的平台,用于从文献中收集和存储毒理学结构警报,并对化学文库进行虚拟筛选,以标记可能具有毒性的化学物质和化合物,这些物质和化合物可能会引起不良反应。警报通过 SMARTS 模板、毒理学终点和描述警报的出版物进行唯一标识。此外,该系统还允许存储补充信息,如名称、注释和作用机制,以及其他数据。最重要的是,该平台可以轻松用于对大型化学数据集、重点库或新设计的化合物进行快速虚拟筛选,针对毒理学警报提供化学物质的详细分组概况,并按结构警报和终点进行分组。这种设施可用于决策是否应通过实验测试化合物,使用现有 QSAR 模型进行验证,或者完全排除该化合物的考虑。基于警报的筛选也有助于更复杂的 QSAR 模型的更轻松解释。该系统是公开的,并且与在线化学建模环境(OCHEM,http://ochem.eu)紧密集成。该系统是开放和可扩展的:任何注册的 OCHEM 用户都可以引入新的警报、浏览、编辑其他用户引入的警报,并针对所有或选定的警报对其数据集进行虚拟筛选。通过结构警报传递的用户设置可用于 OCHEM 的其他典型任务:以多种格式导出、开发 QSAR 模型、根据其他标准进行额外筛选等。该数据库已经包含了近 600 个结构警报,用于诸如致突变性、致癌性、皮肤致敏性、经历代谢激活的化合物、形成反应性代谢物的化合物等终点,这些化合物可能会引起不良反应。ToxAlerts 平台可在 Web 上访问,网址为 http://ochem.eu/alerts,并且它在不断发展壮大。