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Abstract for Miniaturized Luminescent Metabolism Profiling Assays
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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