Slow-Acting Agonist Activity
In a recent presentation, scientists from a large pharmaceutical company summarized studies conducted in their laboratory using the IP-One assay with Gq and Galpha16-coupled receptors.
One of the key findings of the study was the identification, using IP-One, of slow-acting agonist activity not detected by calcium mobilization.
High-throughput screening of this class of compounds may present technological limitations when seeking agonists with the calcium flux, the most commonly used existing HTS method for Gq-protein coupled receptor cell-based functional assays.
Calcium mobilization is a proven and widely used assay. The method can, however, require access to dedicated instrumentation and is limited by its extremely short readout time. These obstacles can increase screening turn-around and can lead to false negatives, particularly when looking for slow-acting agonists. The results presented show evidence of two slow-acting agonists with IP-One, but not with the calcium flux.