Tox Suite

ACD/Tox Suite, developed by ACD/Labs, is a collection of structure-based prediction modules for calculating toxicity and safety endpoints. It is designed for use early in drug discovery workflows, where in silico toxicity screening can help reduce attrition rates by identifying molecular entities unlikely to succeed as drug candidates. The tool is intended for medicinal, synthetic, and research chemists who need to assess toxicity profiles to guide compound synthesis and focus animal testing requirements.

Tox Suite operates as part of the ACD/Labs Percepta platform and supports predictions for single compounds or libraries of tens of thousands of structures. Predictions are based on curated databases of experimental data, and several modules can be trained with in-house experimental data to extend applicability to novel chemical space.

Toxicity Endpoints Covered

• Acute toxicity (LD50 and acute toxicity categories)
• Aquatic toxicity (LC50 for Fathead minnow and Water flea; IGC50 for Ciliate protozoa)
• Endocrine system disruption (estrogen receptor binding affinity)
• Mutagenicity (Ames test probability)
• Adverse health effects on blood, cardiovascular system, gastrointestinal system, kidney, liver, and lungs
• hERG channel inhibition
• Eye and skin irritation (Draize test probability)
• Physicochemical properties including logP, logD, pKa, and aqueous solubility

Prediction and Reliability Features

• Reliability index provided for each prediction to help evaluate confidence in results
• Display of up to five most similar structures from the internal experimental data library, with experimental values and literature references
• Color-mapped structure highlighting to show substructure and atomic contributions to predicted properties (available in select modules)
• Mutagenicity module includes downloadable QMRF and QMRF documents
• hERG inhibition module uses two models — one based on structural descriptors and one based on physicochemical properties — and simulates the influence of different experimental assay types
• Acute toxicity hazard classification aligned with OECD oral acute toxicity hazard categories
• Mutagenicity database browsable for study details, bacterial strains tested, metabolic activation conditions, and other experimental parameters

Structure Input and Data Handling

• Structures can be drawn within the application, entered as SMILES strings or InChI codes, imported from MOL, SK2, SKC, or CDX files, or searched by name using the built-in dictionary
• Supports copy/paste from third-party structure drawing packages
• Activity history allows retrieval of previously calculated results
• Results can be exported to PDF or copied to external applications

Library and Batch Analysis Tools

• Calculate endpoints for compound libraries and use built-in tools to sort, filter, plot, and rank results
• User-defined color-coding of results in spreadsheet view for quick identification of favorable and unfavorable compounds
• Filter results numerically; sort by ascending or descending values
• Create scatter plots to identify trends and prioritize compounds

Lead Optimization and Structure-Property Relationships

• Gain insights into structure-property relationships to guide compound modification
• Good/bad indicators for Lipinski's rule-of-5, lead-likeness, and toxicity endpoints
• Identify structural fragments responsible for hERG inhibition and mutagenicity
• Interactive optimization tool for modifying sets of structures
• Generate libraries of analogs with substituent modifications based on a target property profile
• Sort, filter, and prioritize hundreds of structural analogs
• Create and use custom fragment libraries
• Built-in retrosynthesis tool to target synthetically accessible fragments

Customization and Model Training

• Train prediction algorithms with experimental data in select modules: acute toxicity, aquatic toxicity, mutagenicity, hERG inhibition, logP, logD, and pKa
• Add custom models and in-house prediction algorithms by connecting to an existing web service via XML protocol, or with a DLL (available in thin client deployments)
• Include third-party models alongside built-in and in-house models within a single environment

Workflow Steps

1. Draw or import a structure
2. Select the toxicity property or endpoint of interest
3. Review predicted results, reliability indicators, and similar structure comparisons
4. Copy/paste results or export to PDF for reporting

Tox Suite is available as a desktop/thick client installation on individual computers. It is part of the ACD/Labs Percepta platform, which also supports enterprise deployment. The platform has been adopted by organizations including Merck Germany and Apotex Pharma for in silico prediction of physicochemical, ADME, and toxicity properties in medicinal chemistry and drug candidate optimization workflows.