Titlebook: Optimization in Drug Discovery; Zhengyin Yan,Gary W. Caldwell Book 2004 Humana Press 2004

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In Vitro Identification of UDP-Glucuronosyltransferases (UGTs) Involved in Drug Metabolism,ker activities, and chemical inhibition. The primary focus is on identification of the well-characterized hepatic UGTs, including UGTs 1A1, 1A4, 1A6, 1A9, 2B7, and 2B15, although a similar approach potentially could be used for the study of extrahepatic tissues, such as the kidney and gastrointestinal tract.

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Evaluation of Cytochrome P450 Inhibition in Human Liver Microsomes,C-MS/MS). It is without doubt that results from this in vitro experiment are of great value in lead optimization in drug discovery and development. It is obvious that more efforts are still needed to establish the relevance between in vitro CYP inhibition and drug interactions in the clinic.

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In Vitro Permeation Study With Bovine Brain Microvessel Endothelial Cells,endothelial cells (BMECs) lining the interface between the blood and the brain as the model for screening central nervous system (CNS) drug candidates. The culture procedures and measurement of permeability in BMEC can be applied to other model cell lines such as Caco-2, MDCK, and MDCKII cells.

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Book 2004bsorption, distribution, metabolism, elimination (ADME), and toxicity issues. Lead optimization in drug discovery, a process attempting to uncover and correct these defects of drug candidates, is highly beneficial in lowering the cost and time to develop therapeutic drugs by reducing drug candidate

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pKa, Solubility, and Lipophilicity,ing these three parameters . Because of space limitations, only one method is discussed in detail for each parameter, using chlophedianol as an example. The GLpKa method was used for measuring pK.. The solubility in buffer solutions was measured with liquid chromatography-mass spectrometry (LC-MS) o