Practical application of the ΔΔlog(max/EC50) scale to quantify selectivity

1) Fits dose-response data to function to yield max (maximal response) and EC50Furnishes individual values for log(max/EC50), a single index of agonism
2) Choose a reference agonist for comparison of all test agonists; use the same reference agonist for all systems (receptors, pathways, cell types)Ratios to the index for the reference agonist cancels differences in receptor density, cell sensitivity, assay sensitivity, etc.
3) Calculate Δlog(max/EC50) values for each test agonist (Δlog(max/EC50) = log(max/EC50)ref - log(max/EC50)test)Scales agonist activity of the test agonist to that of the reference agonist within a given system (receptor type, signaling pathway, cell type, etc.)
4) Calculate ΔΔlog(max/EC50) values across the two systems being compared (different receptors, signaling pathways, cell types, protein sequence, etc.) (ΔΔlog(max/EC50) = Δlog(max/EC50)ref – Δlog(max/EC50)test)With the individual differences in sensitivity between the two systems cancelled, ΔΔlog(max/EC50) values provide a system-independent measure of the relative agonism of each test agonist in both systems