In drug development, preclinical safety and pharmacokinetics assessments of candidate drugs to ensure the safety profile are a must. While in vivo and in vitro tests are traditionally used, experimental determinations have disadvantages, as they are usually time-consuming and costly. In silico predictions of these preclinical endpoints have each been developed in the past decades. However, only a few web-based tools have integrated different models to provide a simple one-step platform to help researchers thoroughly evaluate potential drug candidates. To efficiently achieve this approach, a platform for preclinical evaluation must not only predict key ADMET (absorption, distribution, metabolism, excretion and toxicity) properties but also provide some guidance on structural modifications to improve the undesired properties. In this review, we organized and compared several existing integrated web servers that can be adopted in preclinical drug development projects to evaluate the subject of interest. We also introduced our new web server, Virtual Rat, as an alternative choice to profile the properties of drug candidates. In Virtual Rat, we provide not only predictions of important ADMET properties but also possible reasons as to why the model made those structural predictions. Multiple models were implemented into Virtual Rat, including models for predicting human ether-a-go-go-related gene (hERG) inhibition, cytochrome P450 (CYP) inhibition, mutagenicity (Ames test), blood–brain barrier penetration, cytotoxicity and Caco-2 permeability. Virtual Rat is free and has been made publicly available at https://virtualrat.cmdm.tw/.

中文翻译：

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用于药物开发中临床前安全性和药代动力学评估的集成网络服务器的当前开发。

在药物开发中，必须对候选药物进行临床前安全性和药代动力学评估，以确保其安全性。虽然传统上使用体内和体外测试，但实验测定具有缺点，因为它们通常耗时且成本高。电脑模拟这些临床前终点的预测都是在过去几十年中发展起来的。然而，只有少数基于网络的工具集成了不同的模型，以提供一个简单的一步平台来帮助研究人员彻底评估潜在的候选药物。为了有效地实现这种方法，临床前评估平台不仅必须预测关键的 ADMET（吸收、分布、代谢、排泄和毒性）特性，而且还必须对结构修改提供一些指导以改善不需要的特性。在这篇综述中，我们组织并比较了几个现有的集成 Web 服务器，这些服务器可用于临床前药物开发项目以评估感兴趣的主题。我们还推出了我们的新网络服务器 Virtual Rat，作为分析候选药物特性的替代选择。在虚拟老鼠中，我们不仅提供了对重要 ADMET 特性的预测，而且还提供了模型做出这些结构预测的可能原因。在 Virtual Rat 中实施了多种模型，包括预测人类乙醚相关基因 (hERG) 抑制、细胞色素 P450 (CYP) 抑制、致突变性（Ames 试验）、血脑屏障渗透、细胞毒性和 Caco 的模型-2 渗透率。Virtual Rat 是免费的，并已在 https://virtualrat.cmdm.tw/ 上公开提供。血脑屏障渗透、细胞毒性和 Caco-2 渗透性。Virtual Rat 是免费的，并已在 https://virtualrat.cmdm.tw/ 上公开提供。血脑屏障渗透、细胞毒性和 Caco-2 渗透性。Virtual Rat 是免费的，并已在 https://virtualrat.cmdm.tw/ 上公开提供。