Current Status and Perspective of Development of Human in vitro Models for Prediction of Organ Toxicities in the Clinic

Abstract

Despite recent advances in life sciences and large investment in drug discovery research, the success rate of drug development remains low. Since safety accounts for a large percentage of failure of clinical studies, selection of compounds with fewer toxicity concerns is the key to improving the success rate of drug development. However, predicting clinical toxicity from preclinical studies, which mainly use animal models, is still challenging because of species differences. Recently, in vitro models using human cells have been attracting attention to overcome this issue. These novel in vitro models have physiologically relevant functions compared to cell lines traditionally utilized in in vitro assays, thereby enabling us to predict toxicity in humans with high accuracy. Additionally, with the high throughput, these models can be applied from early stages of drug discovery research, thus making it possible to select more promising drug candidates and focus research and development resources on them. In this review, we introduce in vitro models to predict cardiotoxicity and hepatotoxicity, which are two leading causes of clinical failure derived from safety issues.