What Are We Missing? The Detergent Triton X-100 Added to Avoid Compound Aggregation Can Affect Assay Results in an Unpredictable Manner.

In this study we show that the detergent Triton X-100, which is widely used in screening campaigns, significantly decreases the binding affinities of some known specific inhibitors of HIV-1 protease and the well-established model protease endothiapepsin in a fluorescence-based assay. Surprisingly, other structurally related inhibitors remain entirely unaffected. As a consequence, those compounds that were affected would most likely have been misclassified as unspecific binders, although they are actually true positives, and thus could be considered excellent starting points for further hit optimization.