I had originally intended to look at permeability in this post but I do need to respond to Dan Erlanson’s post at Practical Fragments. I see Dan’s position (“everything is an artifact until proven otherwise”) as actually very similar to my position (“chemical probes will have to satisfy the same set of acceptability criteria whether or not they trigger structural alerts”) and we’re both saying that you need to perform the necessary measurements if you’re going to claim that a compound is acceptable for use as a chemical probe. Where Dan’s and my respective positions appear to diverge is that I consider structural alerts based on primary screening output (i.e., % response when assayed at a single concentration) to be of minimal value for assessment of optimized chemical probes. My comment on the “The Ecstasy and Agony of Assay Interference Compounds” editorial should make this position clear.
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