Perloff, E. S. published the artcileValidation of cytochrome P450 time-dependent inhibition assays: a two-time point IC50 shift approach facilitates kinact assay design, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is cytochrome P450 inhibitor liver drug interaction.
Recent guidance from the US Food and Drug Administration (USFDA) has advocated testing of time-dependent inhibition of cytochrome P 450 (CYP), which can be addressed by performing IC50 shift as well as KI/kinact determinations Direct (IC50, Ki) and time-dependent inhibition (IC50 shift, KI/kinact) assays were validated in human liver microsomes with liquid chromatog.-tandem mass spectrometry (LC/MS/MS) anal. for the following enzyme/substrate/inhibitor combinations: CYP1A2/phenacetin/alpha-naphthoflavone/furafylline, CYP2C8/amodiaquine/montelukast/gemfibrozil-1-O-β-glucuronide, CYP2C9/diclofenac/sulfaphenazole/tienilic acid, CYP2C19/S-mephenytoin/S-benzylnirvanol/S-fluoxetine, CYP2D6/dextromethorphan/quinidine/paroxetine, and CYP3A4/midazolam/testosterone/ketoconazole/azamulin/verapamil/diltiazem. IC50 shift assays were performed with two pre-incubation time points (10 and 30 min) to facilitate kinact assay design. Data obtained show good agreement with literature values. For rapid acting inhibitors, such as azamulin/CYP3A4 and tienilic acid/CYP2C9, the IC50 shifts were similar at both time points suggesting a short maximum pre-incubation time with closely spaced time points for the KI/kinact assay. Slow acting inhibitors (such as verapamil/CYP3A4 or S-fluoxetine/CYP2C19) showed an increase in IC50 shift between 10 and 30 min suggesting a longer maximum pre-incubation time with wider spacing of time points for KI/kinact. The two-time point IC50 shift experiment proved to be an excellent method for the selection of appropriate KI/kinact assay parameters and is suitable for the routine anal. of P 450 inhibition by drug candidates.
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, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem