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
Current Pharmaceutical Design
Title: New Insights in Drug-Induced Mitochondrial Toxicity
Volume: 17 Issue: 20
Author(s): Sashi Nadanaciva and Yvonne Will
Affiliation:
Keywords: Mitochondrial toxicity, in vitro assay, drug, compound attrition, glycolysis, ubiquinone, dyslipidemia, oxidative phosphorylation, cations, Valproic acid
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.
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Cite this article as:
Nadanaciva Sashi and Will Yvonne, New Insights in Drug-Induced Mitochondrial Toxicity, Current Pharmaceutical Design 2011; 17 (20) . https://dx.doi.org/10.2174/138161211796904795
DOI https://dx.doi.org/10.2174/138161211796904795 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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