A Novel Lipidomics-Based Approach to Evaluating the Risk of Clinical Hepatotoxicity Potential of Drugs in 3D Human Microtissues

The importance of adsorption, distribution, metabolism excretion and toxicity (ADMET) analysis is expected to grow substantially due to recent failures in detecting severe toxicity issues of new chemical entities during preclinical/clinical development. Traditionally, safety risk assessment studies for humans have been conducted in animals during advanced preclinical or clinical phase of drug development. However, potential drug toxicity in humans now needs to be detected in the drug discovery process as soon as possible without reliance on animal studies. The ‘omics’, such as genomics, proteomics and metabolomics, have recently entered pharmaceutical research in both drug discovery and drug development, but at the best of our knowledge no applications in high-throughput safety risk assessment have been attempted so far. This paper reports an innovative method to anticipate adverse drug effects in an early discovery phase based on lipid fingerprints using human three-dimensional (3D) microtissues. The ris...