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June 19, 2012
Watch Your Cell Assays
I've written here before about the (now) well-known problem of compound aggregation in screening assays. You can get false positives when a compound itself forms a colloidal mass that pulls the target protein into it. The readout looks as if the protein has been inactivated by the small molecule itself, just the way you were hoping for, but if you add a bit of detergent the activity mysteriously goes away.
The Shoichet lab has a paper out that warns people to look out for this in cellular assays as well. This time you'll get false negatives - the colloidal aggregates don't act right compared to the free molecules, as you could well imagine. Update: I see that Wavefunction has covered this same paper! Reformulating the assay restores the activity, but the trick is knowing that there was a problem to start with. Something to keep in mind when your cell assay numbers are wonky (as if there weren't enough reasons for that to happen already).
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