Pathway-specific, species, and sub-type counterscreening for better GPCR hits in high throughput screening.
G protein-coupled receptors represent one of the largest families of drug targets. Time and cost may be saved if GPCR modulators are assessed in terms of signaling pathway selectivity, species selectivity, and selectivity against closely-related family members early in the drug discovery process, perhaps even at the stage of high-throughput screening. Examples are given of how these kinds of selectivity have been addressed during screening.
Swanson
Robert
R
Ligand Pharmaceuticals, 3000 Eastpark Blvd., Cranbury, NJ 08512, USA.
Beasley
James R
JR
D000818:Animals; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D057166:High-Throughput Screening Assays / Q000379:methods* / Q000639:trends; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity
D004364:Pharmaceutical Preparations; D021122:Protein Subunits; D043562:Receptors, G-Protein-Coupled