De-risking seizure liability: integrating adverse outcome pathways (AOPs), new approach methodologies (NAMs), and in silico approaches while highlighting knowledge gaps.

ABSTRACT: Animal studies are commonly used in drug development and in chemical and environmental toxicology to predict human toxicity, but their reliability, particularly in the central nervous system (CNS), is limited. For example, animal models often fail to predict drug-induced seizures, leading to unforeseen convulsions in clinical trials. Evaluating environmental compounds, such as pesticides, also poses challenges due to time and resource constraints, resulting in compounds remaining untested. To address these limitations, a government-industry collaboration identified 27 biological target families linked to seizure mechanisms by combining key events from adverse outcome pathways (AOPs) with drug discovery data. Over a hundred in vitro assay endpoints were identified, covering 26 of the target

SUBMITTER: Behl M 

PROVIDER: S-EPMC12469190 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature