Seite - (000096) - in Biomedical Chemistry: Current Trends and Developments

primary culture of hepatocytes, making them more suitable as a HTS methodology. However as they exhibit some morphological changes regarding in vivo models that must be considered during the analysis of the results. Compounds are quantified after predefined times of incubation by HPLC. Three-dimensional hepatic models Different cells-types besides hepatic cells are seeded in the same scaffold and may include fibroblasts, Kupffer cells, vascular and biliary duct endothelial cells in order to maintain the liver-cells homeostasis. Although allow better cell-cell matrix interactions, resembling better in vivo functions and morphology than cell culture/lines, CYP expression may vary according to experimental conditions. Predict hepatic clearance; Mainly used to predict drug hepatic toxicity. BCRP, breast cancer resistance protein; Caco-2, human colon adenocarcinoma cell line; CYP, cytochrome P450; DDI, drug-drug interaction; HPLC, high performance liquid chromatography; HTS, high throughput screening assay; MDCK, Madin-Darby canine kidney cell line; PAMPA, parallel artificial membrane permeability assay; Papp, apparent permeability; UGT, UDP glucuronosyltransferase. – Relevance: the result of the screen should have good concordance with the corresponding in vivo properties of the drug, requiring validation of the screen with standard compounds of known animal or human performance; – Effectiveness: the cut-off criterion should eliminate a substantial fraction of compounds without eliminating every compound, otherwise the screen would merely add a useless extra step that delays the discovery process;