Drug-induced liver injury (DILI) remains a major challenge in drug development, contributing to late-stage attrition, regulatory delays, and increased development costs. Traditional preclinical models often fail to predict complex, species-specific liver toxicities, limiting confidence in human risk assessment and delaying critical decision-making.
This white paper explores how advanced cross-species 3D liver microtissues can improve mechanistic DILI prediction and support proactive preclinical de-risking strategies. Using the case of amcenestrant, a selective estrogen receptor degrader (SERD) associated with cholestatic liver injury in dogs, the study demonstrates how species-specific 3D InSight™ Liver Microtissues successfully identified the underlying mechanism of toxicity that conventional models failed to detect.
Through transcriptomic analysis and prolonged exposure studies, the advanced in vitro models revealed dog-specific FXR antagonism and altered PXR signaling linked to cholestatic injury, while showing no comparable mechanism in rat or human liver microtissues. The findings highlight the importance of moving beyond short-term cytotoxicity screening toward mechanistic, functional, and transcriptomic assessment.
Learn how integrating advanced 3D liver spheroids into early drug discovery workflows can help identify species-specific liabilities, improve translational confidence, and support safer, more efficient drug development.