Combination of glutathione trapping and time-dependent inhibition assays as a predictive method of drugs generating highly reactive metabolites

نویسندگان

  • Shintaro Nakayama
  • Hideo Takakusa
  • Akiko Watanabe
  • Yoshihiro Miyaji
  • Wataru Suzuki
  • Daisuke Sugiyama
  • Kazuhito Shiosakai
  • Kokichi Honda
  • Noriko Okudaira
  • Takashi Izumi
  • Osamu Okazaki
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

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Combination of glutathione trapping and time-dependent inhibition assays as a predictive method 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...

متن کامل

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 کامل

The protective effect of Nigella sativa against liver injury: a review

Nigella sativa (Family Ranunculaceae) is a widely used medicinal plant throughout the world. N. sativa is referred in the Middle East as a part of an overall holistic approach to health. Pharmacological properties of N. sativa including immune stimulant, hypotensive, anti-inflammatory, anti-cancer, antioxidant, hypoglycemic, spasmolytic and bronchodilator have been shown. Reactive oxygen specie...

متن کامل

Development of a Method for measuring Reactive Oxygen Radicals Levels In Vitro and Study the Effects of Vitamin C and E on Radical Production Reaction

Background: Free radicals and reactive oxygen species(ROS) are the most important factors in formation of oxidative stress reaction. Now, radical damage has been suggested to contribute to a wide variety of diseases such as Alzheimer, atherosclerosis and cancer. Transition metal ions in the presence of the various biomolecules produce these active compounds. The aim of this study is introducing...

متن کامل

Role of Residue 87 in the Activity and Regioselectivity of Clozapine Metabolism by Drug Metabolizing Bm3 M11: Application for Structural Characterization of Clozapine Gsh Conjugates

In the present study, a site-saturation mutagenesis library of drug metabolizing BM3 M11 with all 20 amino acids at position 87 was applied as biocatalyst for the production of stable and reactive metabolites of clozapine. Clozapine is an atypical antipsychotic drug where formation of reactive metabolites is considered to be responsible for several adverse drug reactions. Reactive intermediates...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2011