Titlebook: Cytochrome P450; In Vitro Methods and Zhengyin Yan,Gary W. Caldwell Book 2021 The Editor(s) (if applicable) and The Author(s), under exclus

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Guanhua Wang,Zhuo Fang,Xiaoyuan Xiaal tools to evaluate CYP induction and suppression. As described in this chapter, enzyme induction and suppression can be assessed by measuring P450 enzyme activity as well as mRNA in 3D spheroids culture.

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Characteristics of Major Drug Metabolizing Cytochrome P450 Enzymes, information to investigate the various CYP-related properties of xenobiotics in a drug discovery pipeline. Chapters .–. provide detailed CYP and non-CYP in vitro methods and protocols that can be easily established in drug discovery.

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Evaluation of Time-Dependent Cytochrome P450 Inhibition Using the Area Under the Curve Shift Methodt activity remaining versus the inhibitor concentration plot. By producing in vitro TDI data, clinical DDI can be understood and predicted. In vitro testing helps predict in vivo results, as well as helps in the design or avoidance of clinical trials.

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Assessing Cytochrome P450 Time-Dependent Inhibition (IC50 Shift Assay) Using Both Diluted and Non-D incubation, and a lower concentration of HLMs can be used throughout the experiment. Here we describe both dilution and non-dilution methods to evaluate the time-dependent inhibition against CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 (midazolam and testosterone as substrate) in human liver microsomes.

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Dieter Schallreuter,Eberhard Neumannam instrument where the total P450 enzyme is reduced by sodium dithionite prior to equilibration of the sample with carbon monoxide. Variations on the method to reduce the potentially confounding effects of hemoglobin contamination are also included.