Cell-Based Assays for GPCR Drug Discovery: Focus on Label-free
GPCR Drug Discovery
Lisa Minor, Ph.D. Vascular Research Team Johnson & Johnson PRD LLC
Abstract
Cell-based functional assays are a mandatory component of drug discovery. They are used
across the drug discovery process from: target inception; in target identification to validate
function of a target in a cell's processes; and primary and secondary screening to measure
the effect of a compound on a molecular target's activity, i.e., does it have cellular function at all? If it does, is it an antagonist, an agonist or a positive allosteric modulator? Cellbased assays are also used in the final stages of compound profiling in documenting safety by measuring off-target effects. They can be used to look at many varied targets ranging from cell surface receptors, nuclear receptors, ion channels, enzymes, protein/protein
interactions, as well as a cell's growth and cellular phenotypic responses. Each one of
these applications has numerous assays/assay formats/cell types etc., that are used to measure effects. GPCRs (G protein coupled receptors also known as 7-transmembrane receptors, 7TM) are one of the most predominant and drugable group of molecules in the human genome. Clinical entities targeting GPCRs exist for antipsychotics, antihypertensive,
anticholinergics, anti-diabetics and represent about 30% of marketed human medicines.
Because of the sheer number of various cellbased assays for GPCRs and because of the
importance of GPCRs to drug discovery, the focus of this article will be on assays for GPCRs with special emphasis on the newest technology entry into the drug discovery world; label-free.
This article was published in the February/March 2010 issue of International Drug Discovery, Volume 5, Issue 1, on pgs. 32-36.
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