New Insights in Drug-Induced Mitochondrial Toxicity

Sashi      Nadanaciva; Yvonne      Will

doi:10.2174/138161211796904795

Abstract

Drug-induced mitochondrial toxicity is rapidly gaining recognition within the pharmaceutical industry as a contributor to compound attrition and post-market drug withdrawals. This article describes the mechanisms which lead to drug-induced mitochondrial toxicity, discusses high-throughput in vitro assays which are currently being used to identify mitochondrial dysfunction, and provides an overview on some of the drugs which impair mitochondrial function. While considerable progress has been made in the development of highthroughput assays to screen for mitochondrial impairment in vitro, much remains to be done. This includes the development of in silico models to predict drug-induced mitochondrial impairment, wider acceptance of suitable animal models, identification and validation of relevant biomarkers, and the translation of in vitro/in vivo results to clinical outcomes.

Keywords: Mitochondrial toxicity, in vitro assay, drug, compound attrition, glycolysis, ubiquinone, dyslipidemia, oxidative phosphorylation, cations, Valproic acid