Article
Refine
Year of publication
Document Type
- Article (466) (remove)
Language
- English (466) (remove)
Keywords
- Heparin (3)
- Bacillaceae (2)
- Biotechnological application (2)
- Chemometrics (2)
- IR spectroscopy (2)
- NMR spectroscopy (2)
- Principal component analysis (2)
- Standardization (2)
- Subtilases (2)
- Subtilisin (2)
- bubble column (2)
- methanation (2)
- plug flow reactor (2)
- qNMR (2)
- (Poly)saccharides (1)
- Algal Turf Scrubber (1)
- Algal–bacterial bioflm (1)
- Alginate beads (1)
- Alkalihalobacillus okhensis (1)
- Aloe vera (1)
- Authenticity (1)
- Biofuel (1)
- Biogas (1)
- Biomass (1)
- Biorefinery (1)
- Bragg peak (1)
- Broad pH spectrum (1)
- Butanol (1)
- CRISPR/Cas9 (1)
- Chondroitin sulfate (1)
- Circular bioeconomy (1)
- Clostridium acetobutylicum (1)
- Crude heparin (1)
- Cyclotron production (1)
- Dehydrogenase (1)
- Detergent protease (1)
- Deuterated solvents (1)
- Deuterium NMR (1)
- Diaphorase (1)
- Dietary supplements (1)
- Enzymatic biosensor (1)
- Extracellular enzymes (1)
- Ga-68 (1)
- Glucosamine (1)
- Halotolerant protease (1)
- High-field NMR (1)
- Hypersecretion (1)
- IR (1)
- Inorganic ions (1)
- Ions (1)
- Lignocellulose (1)
- Linear discriminant analysis (1)
- Manufacturer (1)
- Marker-free mutagenesis (1)
- Medical radionuclide production (1)
- Metal contaminants (1)
- Methane (1)
- Microfluidic solvent extraction (1)
- Molecular modelling (1)
- Molecular weight determination (1)
- NMR (1)
- Organic acids (1)
- P2G (1)
- PLS-regression (1)
- Polysaccharides (1)
- Quality control (1)
- Quantum chemistry (1)
- Simultaneous determination (1)
- Soft independent modeling of class analogy (1)
- Spectroscopy (1)
- Stenotrophomonas maltophilia (1)
- Streptomyces griseus (1)
- Streptomyces lividans (1)
- USP (1)
- Uracil-phosphoribosyltransferase (1)
- acetoin (1)
- acetoin reductase (1)
- actuator-sensor system (1)
- alcoholic beverages (1)
- aspergillus (1)
- bacterial cellulose (1)
- bi-enzyme biosensor (1)
- bio-methane (1)
- bioavailability (1)
- biodegradable polymers (1)
- biological dosimeter (1)
- biomethane (1)
- biosensors (1)
- borehole disposal (1)
- capacitive field-effect sensor (1)
- capacitive field-effect sensors (1)
- coculture (1)
- deficit irrigation (1)
- detergent protease (1)
- disposal facility (1)
- drug metabolising enzymes (1)
- drug–drug interactions (1)
- elastomers (1)
- enzyme kinetics (1)
- enzyme-logic gate (1)
- exopolysaccharides (1)
- filamentous fungi (1)
- genome engineering (1)
- geological disposal (1)
- glycine (1)
- halotolerant protease (1)
- high-alkaline subtilisin (1)
- human metabolites (1)
- hydrogel (1)
- hydrogels (1)
- light-addressable electrode (1)
- light-addressable potentiometric sensor (1)
- mechanical properties (1)
- microfluidics (1)
- micronutrients (1)
- neutrons (1)
- nuclear waste (1)
- onion (1)
- optical fibers (1)
- oxidative stable protease (1)
- penicillinase (1)
- polyaspartic acid (1)
- power-to-gas (1)
- prebiotic (1)
- proton therapy (1)
- protons (1)
- pullulan (1)
- recombinant expression (1)
- relative dosimetry (1)
- retention time (1)
- rubber (1)
- superabsorbent polymers (1)
- supramolecular structures (1)
- swelling properties (1)
- theory and modeling (1)
- tobacco mosaic virus (TMV) (1)
- transporters (1)
- urease (1)
- water economy (1)
- yield (1)
- α-aminoacylase (1)
- ε-lysine acylase (1)
Institute
- Fachbereich Chemie und Biotechnologie (466) (remove)
Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.
The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine.