During these assays, compound 66, a tetralin-substituted benzothiazole, showed visible aggregation at high concentrations, raising concern that this compound may be partially inhibiting the enzymes by inducing aggregation. To investigate the risk of aggregation, we assessed some compounds with and without the addition of Triton X-100, a nonionic surfactant which has been previously used in enzymatic assays to prevent colloidal aggregation. When assayed with Triton X-100, compound 66 showed a noticeable reduction in inhibition, though it still showed potent inhibition of PTPs, suggesting that aggregation is partially contributing to the inhibition with this compound. By comparison, compound 74 showed no visible aggregation and likewise retained inhibitory activity towards PTPs in the presence of Triton X-100 (Figure ). These results indicate that future screening and optimization of this class of inhibitors should include a critical evaluation of misleading aggregate-based inhibition.