title: High throughput quantitative assessment of CYP inactivation using 2 concentration points.
abstract: To provide a fast and quantitative assessment of CYP inactivation in the drug discovery stage, a mathematical model was derived to calculate enzyme inactivation parameters, k(inact) and K(I), based on experimental data obtained from 2 concentrations of enzyme inactivator. With CYP3A4 inactivators across a range of inactivation potencies, this novel method provided expected rank-ordering of CYP3A4 inactivation. Furthermore, the k(inact) and K(I) values obtained in the two-concentration format correlate generally well with the parameters obtained in the six-concentration format.
authors: Department of Drug Discovery Support, Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut 06877, USA.
authors: Daniel
authors: D
authors: Albaugh
authors: Thomas
authors: T
authors: Farrell
authors: Michael
authors: M
authors: Langan
authors: W George
authors: WG
authors: Lai
mesh_terms: D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008962:Models, Theoretical
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human