title: High throughput P450 inhibition screens in early drug discovery.
abstract: This review of high throughput (HT) P450 inhibition technologies and their impact on early drug discovery finds the field at a mature stage. The relationship between P450 inhibition and drug-drug interactions is well understood. A wide variety of P450 inhibition detection technologies are readily available off-the-shelf, but what seems still to be missing is a general agreement on how much weight one should give to the various types of early discovery HT P450 inhibition data. Method-dependent potency differences are a cause of concern, and to resolve this issue the authors advocate calibration of the HT methods with a large set of marketed drugs.
authors.affiliation: Chemistry Department, Vertex Pharmaceuticals, San Diego, CA 92121, USA. gregor_zlokarnik@sd.vrtx.com
authors.forename: Gregor
authors.initials: G
authors.lastname: Zlokarnik
authors.forename: Peter D J
authors.initials: PD
authors.lastname: Grootenhuis
authors.forename: John B
authors.initials: JB
authors.lastname: Watson
mesh_terms: D002138:Calibration; D065607:Cytochrome P-450 Enzyme Inhibitors; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods*; D004347:Drug Interactions
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors