Promega Corporation

Miniaturized Luminescent Metabolism Profiling Assays

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Abstract

Tracy Worzella1,  Jean Shieh2, and Aoife Gallagher3
1Promega Corporation, 2800 Woods Hollow Road, Madison, WI 53711, 2Labcyte Inc., 1190 Borregas Ave, Sunnyvale, CA 94089, 3Deerac Fluidics, Unit 8, Enterprise Centre, Pearse St., Dublin, Ireland

Cytochrome P450 and monoamine oxidases are two groups of enzymes involved in the metabolism of drugs. The interactions of these enzymes and compounds are studied carefully in early drug discovery process to facilitate greater success in clinical trials. Promega luminescent metabolism assays consist of the P450-Glo™ Screening Systems for CYP 1A2, 2C9, 3A4, 2C19 and 2D6, as well as the MAO-Glo™ Assay System for monoamine oxidase A. Using the Labcyte® Echo™ 550 acoustic liquid handler and the Deerac Fluidics Equator HTS reagent dispenser, a collection of compounds was profiled by IC50 against the panel of metabolism assays in 1536-well format. Total assay volume of 5 µL was achieved by combining the acoustic technology and non-contact spot-on™ technology. The flexible incubation times of all assays, in addition to the single luminescent endpoint readout, allowed the assays to be run on the same plate and simplified data analysis. Profiling with IC50 determined both potency and selectivity of the test compounds against selected enzymes involved in the drug metabolism process. The exceptional Z’-factor scores, show the flexibility and reliability of Promega assays in conjunction with the Labcyte Echo and the Equator HTS from Deerac Fluidics in a high-throughput situation.

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  • Part# PS006
  • Printed in USA.

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