Parmentier, Yannick published the artcileDirect and quantitative evaluation of the major human CYP contribution (fmCYP) to drug clearance using the in vitro Silensomes model, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is drug metabolism clearance CYP Silensome; Phenotyping; cytochrome; drug–drug interaction; mechanism based inhibitor; metabolism; microsomes.
We have applied the concept of using MBIs to produce CYP-Silensomes to quantify the contribution of the major CYPs to drug metabolism (fmCYP). The target CYPs were extensively and selectivity inhibited by the selected MBIs, while non-target CYPs were inhibited by less than 20% of the homologous control activities. Only CYP2D6-Silensomes exhibited a CYP2B6 inhibition that could be easily and efficiently encountered by subtracting the fmCYP2B6 measured using CYP2B6-Silensomes to adjust the fmCYP2D6.3. To validate the use of a panel of 6 CYP-Silensomes, we showed that the fmCYP values of mono- and multi-CYP metabolized drugs were well predicted, with 70% within ± 15% accuracy. Moreover, the correlation with observed fmCYP values was higher than that for rhCYPs, which were run in parallel using the same drugs (<45% within ±15% accuracy). Moreover, the choice of the RAF substrate in rhCYP predictions was shown to affect the accuracy of the fmCYP measurement. These results support the use of CYP1A2-, CYP2B6-, CYP2C8-, CYP2C9-, CYP2D6 and CYP3A4-Silensomes to accurately predict fmCYP values during the in vitro enzyme phenotyping assays in early, as well as in development, phases of drug development. Xenobiotica 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, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem