Clinically relevant CYP3A4 induction mechanisms and drug screening in 3D spheroid cultures of primary human hepatocytes.
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Clinically relevant CYP3A4 induction mechanisms and drug screening in 3D spheroid cultures of primary human hepatocytes.
CYP3A4 induction is an important cause of drug-drug interactions, making early identification of drug candidates with the obligations CYP3A4 induction in drug development prerequisites. Here, we present a 3D spheroid cultures of primary human hepatocytes (PHH) as CYP3A4 induction of new screening models.
Screening of 25 drugs (12 known inducers of CYP3A4 in vivo and 13 negative control) at physiologically relevant concentrations revealed 100% sensitivity and 100% specificity system. Three of inducers of CYP3A4 in vivo induction of CYP3A4 displayed capacity is much higher in comparison with the 3D spherical culture in 2D monolayer culture. Among them, we identify AZD1208, PIM kinase inhibitor in Phase I development stopped because of unexpected autoinduction CYP3A4, CYP3A4 inducer as the only active in 3D spheroids but not in 2D monolayer culture.
Gene knockdown experiments revealed that AZD1208 require PXR to induce CYP3A4. Rifampicin require PXR solely to induce CYP3A4 and CYP2B6, while phenobarbital-mediated induction of CYPs is not indicative of the absolute dependence on both PXR or CAR demonstrated its ability to switch the activation of nuclear receptors. Mechanistic Study of AZD1208 to find involvement of MAPK / ERK pathway in induction of CYP3A4-sensitive culture format used, as revealed by the inhibition of ERK1 / 2 phosphorylation Tyr204 and sensitivity to EGF pressure. Accordingly, we also identified lapatinib, a dual EGFR / HER2 inhibitor, such as CYP3A4 inducer active just another round in 3D culture.
Our findings offer insight into the pathways involved in the induction of CYP3A4 and suggest spheroids PHH for preclinical screening of CYP3A4 induction.
Clinically relevant CYP3A4 induction mechanisms and drug screening in 3D spheroid cultures of primary human hepatocytes.
Glucose and lipid metabolism screening models of hepatocyte spheroids after culture by injecting fiber fragments.
With the increase in obesity, diabetes and other metabolic diseases, in vitro liver cell and tissue models play an important role in the identification of active pharmaceutical ingredients. Up to now three-dimensional (3D) models rarely focuses on the culture of hepatic glucose and lipid metabolism.
In addition, primary human liver cells suffer from limited availability and differences among donors to build the model reproduced. Thus, in this study, the most available human liver cancer cells (HepG2), and primary hepatocytes from rat (RPH) proposed to build a 3D spheroids using fiber fragments graft syringe with galactose (GSF) as a substrate. RPH and spheroids showed HepG2 cells and cell fragments strong-fiber interaction to promote cell survival, albumin and urea synthesis.
Compared with HepG2 spheroids, spheroids RPH demonstrate strong abilities in terms of consumption of glucose metabolism of glucose, glycogen intracellular content, the level of glucose in gluconeogenesis and sensitivity to the hormone modulators such as insulin and glucagon. On the other hand, HepG2 spheroids displays a strong ability of lipid metabolism in produce significantly higher levels of total cholesterol and triglycerides.
Compared with those who did not fragment the fiber, the GSF-supported 3D culture establish an effective model for in vitro glucose (RPH spheroids) and lipid metabolism (HepG2 spheroids). The model confirmed screening of each enzyme activity and gene expression and showed significantly higher sensitivity and clinically relevant response to hypoglycemic and lipid-lowering drugs.
Description: A competitive ELISA for quantitative measurement of Rat Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Canine Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Canine Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Canine Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Porcine Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Porcine Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Porcine Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Goat Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Goat Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Goat Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Mouse Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Human Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Human Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Human Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rabbit Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rabbit Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rabbit Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Monkey Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Monkey Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Monkey Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Guinea pig Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Guinea pig Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Guinea pig Primary hepatic carcinoma in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Wistar Rat Bone Marrow Mesenchymal Stem Cells With GFP
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Growth Factor in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Growth Factor in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Growth Factor in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Rat Hepatocyte Growth Factor (HGF) in serum, plasma, tissue homogenates, cell culture supernates and other biological fluids.
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Rat Hepatocyte Growth Factor (HGF) in serum, plasma, tissue homogenates, cell culture supernates and other biological fluids.
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Rat Hepatocyte Growth Factor (HGF) in serum, plasma, tissue homogenates, cell culture supernates and other biological fluids.
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Rat Hepatocyte Growth Factor (HGF) in serum, plasma, tissue homogenates, cell culture supernates and other biological fluids.
Description: Double-antibody Sandwich chemiluminescent immunoassay for detection of Rat Hepatocyte Growth Factor (HGF)Serum, plasma, tissue homogenates, cell culture supernates and other biological fluids
Description: A sandwich quantitative ELISA assay kit for detection of Rat Hepatocyte Growth Factor (HGF) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: A sandwich quantitative ELISA assay kit for detection of Rat Hepatocyte Growth Factor (HGF) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates or other biological fluids.
Description: Quantitativesandwich ELISA kit for measuring Rat hepatocyte growth factor, HGF in samples from serum, plasma, tissue homogenates. A new trial version of the kit, which allows you to test the kit in your application at a reasonable price.
Description: Quantitativesandwich ELISA kit for measuring Rat hepatocyte growth factor, HGF in samples from serum, plasma, tissue homogenates. Now available in a cost efficient pack of 5 plates of 96 wells each, conveniently packed along with the other reagents in 5 separate kits.
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Hepatocyte Growth Factor (HGF) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Hepatocyte Growth Factor (HGF) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Hepatocyte Growth Factor (HGF) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Hepatocyte Growth Factor (HGF) in serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids.
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Rat Hepatocyte Growth Factor (HGF) in samples from serum, plasma, tissue homogenates, cell lysates, cell culture supernates and other biological fluids with no significant corss-reactivity with analogues from other species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 1 β in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 1 β in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 1 β in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 6 β in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 6 β in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 6 β in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: Quantitative sandwich ELISA for measuring Rat Hepatocyte growth factor (HGF) in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids.
Description: Quantitative sandwich ELISA for measuring Rat Hepatocyte growth factor (HGF) in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids.
Description: Quantitative sandwich ELISA for measuring Rat Hepatocyte growth factor (HGF) in samples from cell culture supernatants, serum, whole blood, plasma and other biological fluids.
Description: A sandwich ELISA kit for detection of Hepatocyte Growth Factor from Rat in samples from blood, serum, plasma, cell culture fluid and other biological fluids.
Rat Hepatocyte Growth Factor Like (MST1) ELISA Kit
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 1 Alpha in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 1 Alpha in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 1 Alpha in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 4 Alpha in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 4 Alpha in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 4 Alpha in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 6 Alpha in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 6 Alpha in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A competitive ELISA for quantitative measurement of Rat Hepatocyte Nuclear Factor 6 Alpha in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Hepatocyte growth factor receptor in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Hepatocyte growth factor receptor in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Description: A sandwich ELISA for quantitative measurement of Rat Hepatocyte growth factor receptor in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species.
Rat Hepatocyte Nuclear Factor 1 Beta (HNF1b) CLIA Kit
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Rat Hepatocyte Nuclear Factor 1 Beta (HNF1b) in Tissue homogenates and other biological fluids.
Rat Hepatocyte Nuclear Factor 1 Beta (HNF1b)CLIA Kit
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Rat Hepatocyte Nuclear Factor 1 Beta (HNF1b) in Tissue homogenates and other biological fluids.
Rat Hepatocyte Nuclear Factor 1 Beta (HNF1b)CLIA Kit
Description: This is Double-antibody Sandwich Chemiluminescent immunoassay for detection of Rat Hepatocyte Nuclear Factor 1 Beta (HNF1b) in Tissue homogenates and other biological fluids.
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Thus, the culture configuration shows the predicted in vitro platform for defining the profiles of glucose and lipid metabolism and screening of therapeutic agents for metabolic disorders such as diabetes and obesity.
