Dahlinger, Dominik published the artcileDevelopment and validation of an in vitro, seven-in-one human cytochrome P 450 assay for evaluation of both direct and time-dependent inhibition, Formula: C13H8Cl2O4S, the main research area is cytochrome P450 isoform human assay time dependent inhibition validation; Cytochrome P450; Drug–drug interactions; Methods; N-in-one; Single point inactivation; Time-dependent inhibition.
Direct and time-dependent inhibition (TDI) of cytochrome P 450 (CYP) isoforms raises drug safety concerns and has major implications in drug development. This study describes the development of a liquid chromatog.-tandem mass spectrometry (LC-MS/MS)-based screening tool to simultaneously assess both the direct and the time-dependent inhibitory potential of xenobiotics on the 7 major CYPs using a 2-step approach. The in vitro cocktail of FDA-recognized model substrates was incubated with human liver microsomes (HLM) and consisted of caffeine (CYP1A2), bupropion (CYP2B6), rosiglitazone (CYP2C8), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A4). Direct and time-dependent inhibitory profiles of direct and time-dependent reference inhibitors for each CYP were studied. For validation, the results were compared to those obtained with the traditional single substrate approach. Statistical uncertainty was quantified using the bootstrap method. The direct inhibition assay showed an acceptable fold bias of 1.35 (geometric mean fold absolute deviation, range 1.01-2.61) in the IC50 values for the cocktail assay compared to the single substrate results with no trend for under- or overestn. Using a single point inactivation assay to assess TDI, the authors were able to identify all 7 tested time-dependent reference inhibitors, without any false negatives. The presented design enhanced throughput by assessing the 7 major CYPs simultaneously and allowed for the detection of and discrimination between direct and time-dependent CYP inhibition via IC50 and single point inactivation experiments For the latter, a threshold of 10% TDI was proposed for carrying out more detailed inactivation kinetic experiments
Journal of Pharmacological and Toxicological Methods published new progress about Drug interactions. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Formula: C13H8Cl2O4S.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem