In vitro hepatotoxicity testing in the early phase of drug discovery

With remarkable advancement both in drug discovery, R&D activities and in concomitant technical supports, drug discovery strategies have become focused on drug safety screening in their early stages. The phenomenon suggests the necessity of evaluating toxicity of various compounds with small amounts of their samples as quickly as possible. This series of toxicological strategies is now commonly called "HighThroughput Toxicology", an essential part of toxicological study in the early phase of drug discovery, and particularly hepatotoxicity is one of key issues for drug safety evaluation to select the candidate compounds for new drug. In-vitro evaluation system as a screening system plays an important role in the early phase of pharmaceutical development. They are also important to clarify the mechanisms of toxicity observed during development. Toxicopanomics technologies (a collective designation for the "-omics" such as toxicogenomics, toxicoproteomics and metabonomics) is expected to be applicable to predictive toxicology and mechanism-based risk assessment. Currently, toxicopanomics technology is being applied to the development of new in-vitro safety evaluation systems. In this paper, we will introduce in-vitro hepatotoxicity screening tests, and show the correlations between in-vitro and in-vivo systems and its application of toxicopanomics technologies to in-vitro safety evaluation systems including toxicologically responsible biomarkers.