A5051159943- Pharmacogenetics and Drug Metabolism
- Analytical Chemistry and Chromatography
- Steroid Chemistry and Biochemistry
- Computational Drug Discovery Methods
- Estrogen and related hormone effects
- Innovative Microfluidic and Catalytic Techniques Innovation
- Effects and risks of endocrine disrupting chemicals
- Mycotoxins in Agriculture and Food
- Pharmaceutical and Antibiotic Environmental Impacts
- Biosimilars and Bioanalytical Methods
- Hormonal Regulation and Hypertension
- Vanadium and Halogenation Chemistry
- Reproductive biology and impacts on aquatic species
- Cholinesterase and Neurodegenerative Diseases
- Synthesis and Biological Evaluation
- Skin Protection and Aging
- Pesticide Exposure and Toxicity
- Hormonal and reproductive studies
- Metabolomics and Mass Spectrometry Studies
- Nitric Oxide and Endothelin Effects
- melanin and skin pigmentation
- Cancer Treatment and Pharmacology
- Receptor Mechanisms and Signaling
- Thyroid Disorders and Treatments
- Olfactory and Sensory Function Studies
Charles River Laboratories (Netherlands)
2018-2024
Charles River Laboratories (United States)
2019
Robert Bosch (United States)
2019
Vrije Universiteit Amsterdam
2005-2016
Society of Environmental Toxicology and Chemistry
2010
In the present study, diversity of a library drug-metabolizing bacterial cytochrome P450 (P450) BM3 mutants was evaluated by liquid chromatography-mass spectrometry (LC-MS)-based screening method. A strategy designed to identify minimal set that displays differences in regio- and stereoselectivities is suitable metabolize large fraction drug chemistry space. We first screened activities six structurally diverse toward 43 marketed drugs (encompassing wide range human phenotypes, cLogP values,...
A fluorescence-based continuous-flow enzyme affinity detection (EAD) setup was used to screen cytochrome P450 BM3 mutants on-line for diversity. The flow-injection screening assay is based on the BM3-mediated O-dealkylation of alkoxyresorufins forming highly fluorescent product resorufin, and can be in different configurations, namely injection ligands, enzymes substrates. Screening conditions were optimized activity a library 32 towards recently synthesized new probe substrate...
Tri-ortho-cresyl phosphate (ToCP) is a multipurpose organophosphorus compound that neurotoxic and suspected to be involved in aerotoxic syndrome humans. It has been reported not ToCP itself but metabolite of ToCP, namely, 2-(ortho-cresyl)-4H-1,2,3-benzodioxaphosphoran-2-one (CBDP), may responsible for this effect as it can irreversibly bind human butyrylcholinesterase (BuChE) acetylcholinesterase (AChE). The bioactivation into CBDP involves Cytochrome P450s (P450s). However, the individual...
We describe the development and validation of a high-resolution screening (HRS) platform which couples gradient reversed-phase high-performance liquid chromatography (RP-HPLC) on-line to estrogen receptor α (ERα) affinity detection using fluorescence polarization (FP). FP, allows at high wavelengths, limits occurrence interference from autofluorescence test compounds in bioassay. A fluorescein-labeled estradiol derivative (E2-F) was synthesized binding assay optimized platereader format....
The estrogenic mycotoxin zearalenone (ZEN) can undergo hepatic reductive metabolism to form the α and β isomers of zearalenol. ZEN also undergoes cytochrome P450 monooxygenase (P450)-mediated oxidative monohydroxylated products, but until now nothing is known about potency these metabolites. This study aimed at investigating by different isoforms determine estrogen receptor (ERα) affinities in vitro P450-generated metabolites an online high-resolution screening (HRS) setup. Human liver...
A novel methodology is presented to investigate the organic solvent tolerability of cytochrome P450 monooxygenase BM3 (CYP BM3) mutants. fluorescence-based continuous-flow enzyme activity detection (EAD) setup was used screen CYP mutants in presence solvents. The based on BM3-mediated O-dealkylation benzyloxyresorufin form highly fluorescent product resorufin. assay not only allows formed resorufin, but it also simultaneously monitors cofactor depletion online. EAD test a small library...
In the present study, validity of using a cocktail screening method in combination with chemometrical data mining approach to evaluate metabolic activity and diversity drug-metabolizing bacterial Cytochrome P450 (CYP) BM3 mutants was investigated. addition, concept utilizing an in-house-developed library CYP as unique biocatalytic synthetic tool support medicinal chemistry evaluated. Metabolic efficiency mutant towards selection model substrates, being amitriptyline (AMI), buspirone (BUS),...
Drug-induced phototoxicity occurs when drugs absorb natural sunlight, leading to chemical reactions causing cellular damage. Distribution light-exposed tissues is critical and enhanced by binding melanin. The International Council on Harmonization S10 guidance document photosafety evaluation of pharmaceuticals states that although nonpigmented skin tends be more sensitive than pigmented skin, models should considered for bind significantly In this study, an in vitro melanin-binding assay was...