Hepatotoxicity poses a critical challenge in drug discovery, often leading to failures and adverse reactions. Understanding liver toxicity mechanisms is crucial, yet designing non-hepatotoxic molecules remains elusive. The absence of a universal in vitro screening approach delays early identification of hepatotoxic compounds, necessitating more efficient drug toxicity assessment methods. Omic approaches, including cytomics, metabonomics, proteomics, and toxicogenomics, offer promising avenues for delineating hepatotoxicity patterns and detecting adverse effects early in the drug development process.

To address these challenges, suitable drug-induced liver injury (DILI) models are essential. Current models, although informative, often fall short in fully elucidating DILI mechanisms. Robust in vitro multiparametric screening assays covering key effects are needed to enhance predictive capacity for human hepatotoxicity and expedite drug development. While hepatotoxicity rarely halts preclinical drug development due to detectability through serum enzyme tests, it may prompt project termination, emphasizing the need for secondary screening approaches if analogs are available.

In summary, a systematic selection of endpoints and the development of advanced in vitro multiparametric screening assays are vital for early hepatotoxicity detection and accelerated drug development. By improving our understanding of liver toxicity mechanisms and enhancing predictive capacity, we can mitigate risks and ensure the safety of pharmaceutical interventions.

Watch this webinar to learn about:

• Advancing Drug Development and Precision Medicine: Harnessing Human Biomimetic Liver Microphysiology Systems (MPS)
• Predicting Human Hepatotoxicity: Modeling with Liver MPS Technology
• Enhancing Drug Clearance Prediction: Human Hepatotoxicity Modeling with Liver MPS
• Validating Data and Translating Findings: Bridging the Gap between Organ-on-Chips and Human Physiology