Author: Feng, Joy Y
Title: Addressing the selectivity and toxicity of antiviral nucleosides Document date: 2018_3_13
ID: uajl5wyk_17
Snippet: Anti-viral nucleoside/tide analogs target the viral DNA and RNA replication machinery, and this mechanism makes them potential inhibitors of host DNA and RNA synthesis as well, especially mitochondrial DNA and RNA synthesis. Mitochondrial toxicity manifests in multiple forms in vivo and underlies many clinical-stage failures and has been difficult to detect in animal studies. Over the past 30 years, a battery of in vitro tests for mitochondrial t.....
Document: Anti-viral nucleoside/tide analogs target the viral DNA and RNA replication machinery, and this mechanism makes them potential inhibitors of host DNA and RNA synthesis as well, especially mitochondrial DNA and RNA synthesis. Mitochondrial toxicity manifests in multiple forms in vivo and underlies many clinical-stage failures and has been difficult to detect in animal studies. Over the past 30 years, a battery of in vitro tests for mitochondrial toxicity has evolved and continues to expand, allowing for improved early detection of mitochondrial liability. As for any drug molecule, the actual toxicity liability cannot be assessed fully until tested in animal toxicity studies and eventually in human clinical trials. Nevertheless, we believe that employing the proper biochemical and cellular assays early on will have a meaningful impact on reducing pre-clinical and clinical toxicity liability for this class of compounds.
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