Mechanism-Based Inhibition: Deriving KI and kinact Directly from Time-Dependent IC50 Values
نویسندگان
چکیده
منابع مشابه
Mechanism-based inhibition: deriving K(I) and k(inact) directly from time-dependent IC(50) values.
The potential of enzyme inhibition of a drug is frequently quantified in terms of IC(50) values. Although this is a suitable quantity for reversible inhibitors, concerns arise when dealing with irreversible or mechanism-based inhibitors (MBIs). IC(50) values of MBIs are time dependent, causing serious problems when aiming at ranking different compounds with respect to their inhibitory potential...
متن کاملIC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of enzyme activity and ligand binding
A new web-server tool estimates K(i) values from experimentally determined IC(50) values for inhibitors of enzymes and of binding reactions between macromolecules (e.g. proteins, polynucleic acids) and ligands. This converter was developed to enable end users to help gauge the quality of the underlying assumptions used in these calculations which depend on the type of mechanism of inhibitor act...
متن کاملAutomated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis.
Increasing reports of time-dependent inhibition of cytochrome P450 (P450) suggest further emphasis on interpreting the consequences, either from a pharmacokinetic or toxicological perspective. Two automated, time-dependent inhibition assays with a liquid chromatography-tandem mass spectrometric endpoint are presented. The initial assay utilizes human liver microsomes, a single concentration of ...
متن کاملDmd065623 1661..1669
In this study, IC50 shift and time-dependent inhibition (TDI) experimentswere carried out tomeasure the ability of amiodarone (AMIO), and its circulating human metabolites, to reversibly and irreversibly inhibit CYP1A2, CYP2C9, CYP2D6, and CYP3A4 activities in human liver microsomes. The [I]u/Ki,u values were calculated and used to predict in vivo AMIO drug-drug interactions (DDIs) for pharmace...
متن کاملInhibitory Effects of Dimethyllirioresinol, Epimagnolin A, Eudesmin, Fargesin, and Magnolin on Cytochrome P450 Enzyme Activities in Human Liver Microsomes
Magnolin, epimagnolin A, dimethyllirioresinol, eudesmin, and fargesin are pharmacologically active tetrahydrofurofuranoid lignans found in Flos Magnoliae. The inhibitory potentials of dimethyllirioresinol, epimagnolin A, eudesmin, fargesin, and magnolin on eight major human cytochrome P450 (CYP) enzyme activities in human liver microsomes were evaluated using liquid chromatography-tandem mass s...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Biomolecular Screening
سال: 2009
ISSN: 1087-0571,1552-454X
DOI: 10.1177/1087057109336751