Integrative functional assays, chemical genomics and high throughput screening: harnessing signal transduction pathways to a common HTS readout.
Chemical genomics is a drug discovery strategy that relies heavily on high-throughput screening (HTS) and therefore benefits from functional assay platforms that allow HTS against all relevant genomic targets. Receptor Selection and Amplification Technology (R-SAT) is a cell-based, high-throughput functional assay where the receptor stimulus is translated into a measurable cellular response through an extensive signaling cascade occurring over several days. The large biological and chronological separation of stimulus from response provides numerous opportunities for enabling assays and increasing assay sensitivity. Here we review strategies for building homogeneous assay platforms across large gene families by redirecting and/or amplifying signal transduction pathways.
Burstein
Ethan S
ES
ACADIA Pharmaceuticals, Inc., 3911 Sorrento Valley Blvd., San Diego, CA 92121, USA. eburstein@acadia-pharm.com
Piu
Fabrice
F
Ma
Jian-Nong
JN
Weissman
Jacques T
JT
Currier
Erika A
EA
Nash
Norman R
NR
Weiner
David M
DM
Spalding
Tracy A
TA
Schiffer
Hans H
HH
Del Tredici
Andria L
AL
Brann
Mark R
MR
D000818:Animals; D023281:Genomics; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction
D043562:Receptors, G-Protein-Coupled