Feitosa Francisco L, F Cabral Victoria, Sanches Igor H, Silva-Mendonca Sabrina, Borba Joyce V V B, Braga Rodolpho C, Andrade Carolina Horta
Laboratory for Molecular Modeling and Drug Design (LabMol), Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, Goiás 74605-220, Brazil.
Center for the Research and Advancement in Fragments and molecular Targets (CRAFT), School of Pharmaceutical Sciences at Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 05508-220, Brazil.
J Chem Inf Model. 2024 Dec 23;64(24):9056-9062. doi: 10.1021/acs.jcim.4c01811. Epub 2024 Dec 11.
Cytotoxicity is essential in drug discovery, enabling early evaluation of toxic compounds during screenings to minimize toxicological risks. assays support high-throughput screening, allowing for efficient detection of toxic substances while considerably reducing the need for animal testing. Additionally, AI-based Quantitative Structure-Activity Relationship (AI-QSAR) models enhance early stage predictions by assessing the cytotoxic potential of molecular structures, which helps prioritize low-risk compounds for further validation. We present a freely accessible web application designed for identifying potential cytotoxic compounds utilizing QSAR models. This application utilizes machine learning techniques and is built on a data set of approximately 90,000 compounds, evaluated against two cell lines, 3T3 and HEK 293. Users can interact with the app by inputting a SMILES representation, uploading CSV or SDF files, or sketching molecules. The output includes a binary prediction for each cell line, a confidence percentage, and an explainable AI (XAI) analysis. Cyto-Safe web-app version 1.0 is available at http://insightai.labmol.com.br/.
细胞毒性在药物发现中至关重要，能够在筛选过程中对有毒化合物进行早期评估，以将毒理学风险降至最低。细胞毒性检测支持高通量筛选，能够有效检测有毒物质，同时大幅减少动物试验的需求。此外，基于人工智能的定量构效关系（AI-QSAR）模型通过评估分子结构的细胞毒性潜力来增强早期预测，这有助于对低风险化合物进行优先级排序以便进一步验证。我们展示了一个可免费访问的网络应用程序，该程序利用QSAR模型来识别潜在的细胞毒性化合物。此应用程序利用机器学习技术，基于约90000种化合物的数据集构建，针对两种细胞系3T3和HEK 293进行评估。用户可以通过输入SMILES表示、上传CSV或SDF文件或绘制分子结构与该应用程序进行交互。输出结果包括针对每个细胞系的二元预测、置信度百分比以及可解释人工智能（XAI）分析。Cyto-Safe网络应用程序1.0版本可在http://insightai.labmol.com.br/获取。
