Combination of glutathione trapping and time-dependent inhibition assays as a predictive method drugs generating highly reactive metabolites
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چکیده
Drug Metabolism and Pharmacokinetics Research Laboratories (S.N., H.T., A.W., Y.M., W.S., D.S., T.I.), Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan Clinical Data and Biostatistics Department (K.S., K.H.), Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan R&D Planning Department (O.O.), Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan DMD Fast Forward. Published on April 5, 2011 as doi:10.1124/dmd.111.039180
منابع مشابه
Combination of GSH trapping and time-dependent inhibition assays as a predictive method of drugs generating highly reactive metabolites.
Covalent binding (CB) of reactive metabolites (RMs) is potentially involved in severe adverse drug reactions. Because the CB assay is of low throughput and costly, a qualitative trapping assay using agents such as [(35)S]GSH is often performed in the early stages of drug discovery. However, trapping methods alone cannot replace the CB assay. We hypothesized that the time-dependent inhibition (T...
متن کاملCombination of glutathione trapping and time-dependent inhibition assays as a predictive method of drugs generating highly reactive metabolites
Drug Metabolism and Pharmacokinetics Research Laboratories (S.N., H.T., A.W., Y.M., W.S., D.S., T.I.), Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan Clinical Data and Biostatistics Department (K.S., K.H.), Daiichi Sankyo Co., Ltd., 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan R&D Planning Department (O.O.), Daiichi Sankyo Co., Ltd., 1-2-58, Hiromac...
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In some cases, the formation of reactive species from the metabolism of xenobiotics has been linked to toxicity and therefore it is imperative to detect potential bioactivation for candidate drugs during drug discovery. Reactive species can covalently bind to trapping agents in in vitro incubations of compound with human liver microsomes (HLM) fortified with β-nicotinamide adenine dinucleotide ...
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تاریخ انتشار 2011