Cyto-Safe: A Machine Learning Tool for Early Identification of Cytotoxic Compounds in Drug Discovery

J Chem Inf Model. 2024 Dec 23;64(24):9056-9062. doi: 10.1021/acs.jcim.4c01811. Epub 2024 Dec 11.

Abstract

Cytotoxicity is essential in drug discovery, enabling early evaluation of toxic compounds during screenings to minimize toxicological risks. In vitro 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/.

MeSH terms

  • 3T3 Cells
  • Animals
  • Drug Discovery* / methods
  • HEK293 Cells
  • Humans
  • Machine Learning*
  • Mice
  • Quantitative Structure-Activity Relationship*
  • Software