title: High throughput metabolic stability screen for lead optimization in drug discovery.
abstract: A high throughput approach for the determination of in vitro metabolic stability and metabolic profiles of drug candidates has been developed. This approach comprises the combination of a Biomek FX liquid handling system with 96-channel pipetting capability and a custom-designed 96-well format on-line incubator with efficient thermal conductivity. This combination facilitates automated reagent preparation, sample incubation, and sample purification for microsome stability studies. The overall process is both fast and accurate and meets the challenges of high throughput screening for drug discovery. A custom designed, user-friendly computer program has been incorporated for large-scale data processing and report generation. Several applications are discussed that implement this strategy for rapid selection of compounds in early drug discovery.
authors.affiliation: Basic Chemistry, Merck Research Laboratory, Merck & Co. Inc., P.O. Box 2000, RY800-B205, Rahway, NJ 07065, USA. sharon_tong@merck.com
authors.forename: Xinchun S
authors.initials: XS
authors.lastname: Tong
authors.forename: Suoyu
authors.initials: S
authors.lastname: Xu
authors.forename: Song
authors.initials: S
authors.lastname: Zheng
authors.forename: James V
authors.initials: JV
authors.lastname: Pivnichny
authors.forename: Jesus
authors.initials: J
authors.lastname: Martin
authors.forename: Claude
authors.initials: C
authors.lastname: Dufresne
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D015195:Drug Design; D006801:Humans; D013058:Mass Spectrometry; D008862:Microsomes, Liver; D015203:Reproducibility of Results