کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2603168 1133810 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Target identification of drug induced mitochondrial toxicity using immunocapture based OXPHOS activity assays
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Target identification of drug induced mitochondrial toxicity using immunocapture based OXPHOS activity assays
چکیده انگلیسی

Mitochondrial dysfunction has been shown to be a pharmacotoxicological response to a variety of currently-marketed drugs. In order to reduce attrition due to mitochondrial toxicity, high throughput-applicable screens are needed for early stage drug discovery. We describe, here, a set of immunocapture based assays to identify compounds that directly inhibit four of the oxidative phosphorylation (OXPHOS) complexes: I, II, IV, and V. Intra- and inter-assay variation were determined and specificity tested by using classical mitochondrial inhibitors. Twenty drugs, some with known mitochondrial toxicity and others with no known mitochondrial liability, were studied. Direct inhibition of one or more of the OXPHOS complexes was identified for many of the drugs. Novel information was obtained for several drugs including ones with previously unknown effects on oxidative phosphorylation. A major advantage of the immunocapture approach is that it can be used throughout drug screening from early compound evaluation to clinical trials.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 21, Issue 5, August 2007, Pages 902–911
نویسندگان
, , , , ,