. Selective modulation of amyloid-beta peptide degradation by flurbiprofen, fenofibrate, and related compounds regulates Abeta levels. J Neurochem. 2009 Nov;111(3):683-95. PubMed.

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  1. The results are noteworthy. However, how do these findings relate to the activity of γ-secretase modulators in reconstituted assays? Moreover, the statement that "flurbiprofen remains one of the most potent SALAs reported" is simply wrong. At an IC50 between 200-300 uM flurbiprofen is one of the weakest SALAs known.

    The findings for the flurbiprofen esters are truly remarkable, as small esters (methyl, ethyl) are readily metabolized to free flurbiprofen. Both flurbiprofen and fenofibrate have to be applied well above their therapeutic concentrations, therefore these findings may not be relevant for AD. However, if these findings can be replicated with GSM-1 or other potent GSMs, they will pose a caveat for GSM assays and further GSM development.