Inhibition of Neural Crest Cell Migration by Strobilurin Fungicides and Other Mitochondrial Toxicants.

Cell-based test methods with a phenotypic readout are frequently used for toxicity screening. However, guidance on how to validate the hits and how to integrate this information with other data for purposes of risk assessment is missing. We present here such a procedure and exemplify it with a case study on neural crest cell (NCC)-based developmental toxicity of picoxystrobin.

Computational Strategies for Assessing Adverse Outcome Pathways: Hepatic Steatosis as a Case Study.

The evolving landscape of chemical risk assessment is increasingly focused on developing tiered, mechanistically driven approaches that avoid the use of animal experiments. In this context, adverse outcome pathways have gained importance for evaluating various types of chemical-induced toxicity. Using hepatic steatosis as a case study, this review explores the use of diverse computational techniques, such as structure-activity relationship models, quantitative structure-activity relationship models, read-across methods, omics data analysis, and structure-based approaches to fill data gaps within adverse outcome pathway networks.

Advancing drug discovery through assay development: a survey of tool compounds within the human solute carrier superfamily.

With over 450 genes, solute carriers (SLCs) constitute the largest transporter superfamily responsible for the uptake and efflux of nutrients, metabolites, and xenobiotics in human cells. SLCs are associated with a wide variety of human diseases, including cancer, diabetes, and metabolic and neurological disorders. They represent an important therapeutic target class that remains only partly exploited as therapeutics that target SLCs are scarce.

ProteoMutaMetrics: machine learning approaches for solute carrier family 6 mutation pathogenicity prediction.

The solute carrier transporter family 6 (SLC6) is of key interest for their critical role in the transport of small amino acids or amino acid-like molecules. Their dysfunction is strongly associated with human diseases such as including schizophrenia, depression, and Parkinson's disease. Linking single point mutations to disease may support insights into the structure-function relationship of these transporters.