Berry, Loren M. published the artcileDynamic modeling of cytochrome P450 inhibition in vitro: impact of inhibitor depletion on IC50 shift, HPLC of Formula: 40180-04-9, the main research area is CYP3A4 CYP2C9 CYP2D6 protein inhibitor liver microsome clarithromycin dasatinib.
The impact of inhibitor depletion on the determination of shifted IC50 (IC50 determined after 30 min of preincubation with inhibitor) is examined In addition, IC50-shift data are analyzed using a mechanistic model that incorporates the processes of inhibitor depletion, as well as reversible and time-dependent inhibition. Anomalies such as a smaller-than-expected shift in IC50 and even increases in IC50 with preincubation were explained by the depletion of inhibitor during the preincubation. The IC50-shift assay remains a viable approach to characterizing a wide range of reversible and time-dependent inhibitors. However, as with more traditional time-dependent inactivation methods, it is recommended that IC50-shift exptl. data be interpreted with some knowledge of the magnitude of inhibitor depletion. For the most realistic classification of time-dependent inhibitors using IC50-shift methods, shifted IC50 should be calculated using observed inhibitor concentrations at the end of the incubation rather than nominal inhibitor concentrations Finally, a mechanistic model that includes key processes, such as competitive inhibition, enzyme inactivation, and inhibitor depletion, can be used to describe accurately the observed IC50 and shifted IC50 curves. For compounds showing an IC50 fold shift >1.5 based on the observed inhibitor concentrations, reanalyzing the IC50-shift data using the mechanistic model appeared to allow for reasonable estimation of KI, KI, and kinact directly from the IC50 shift experiments
Drug Metabolism & Disposition published new progress about Drug metabolism. 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, HPLC of Formula: 40180-04-9.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem