Toxicity is one of the major reasons for late stage attrition in drug development. Companies implement organ toxicity strategies to be applied in drug development, but some molecular and cellular toxicities underlay multiple organ toxicities. Mitochondrial toxicity is known to induce drug induced liver and cardiac injury, the main organ toxicities responsible for toxicity related attrition rates. Real-time cell-based bioenergetics assessment for mitochondrial toxicity can be part of the battery of safety screening assays in early drug development phases. This talk assesses the Seahorse XF platform as a tool for screening mitochondrial dysfunction and presents a workflow with reference to a panel of mitochondrial toxic drugs.
In this webinar we will discuss:
- Context on why and when mitochondrial toxicity should be screened for in early stages of drug development
- Clear cut-offs and rules are detailed
- Discussion on the results obtained with 23 reference drugs, including 4 pairs of of drugs which are structurally related but associated with different DILI concerns in human.
Karen’s recently published research presented was conducted at UCB Pharma SPRL, Developmental Sciences, Investigative Toxicology, Belgium as part of the European Innovative Medicines Initiative (IMI) Program MIP-DILI consortia.