γ-Secretase Inhibitor XXV, FT-9

FT-9, a cell-permeable NSAID-like compound, is a partially selective γ-Secretase Inhibitor in both microsomes and whole cells. Displays dose-dependent inhibition of the γ-secretase cleavage of β-Amyloid Precursor Protein (APP) and APLP2 with IC₅₀ values against APP ICD (intracellular domain) and APLP2 ICD of ˜260 µM, but there is a less potent effect on γ-secretase processing of APLP1. The concentration of FT-9 required to cause a 2-fold increase in APP CTFs, 3.4 +/- 0.4 µM, is significantly lower than that for APLP1 (25.7 +/- 8.9 µM) (P = 0.001). For comparison, the concentration of another γ-Secretase inhibitor compound E (EMD Chemicals, Inc. Cat. No. 565790) needed for a 2-fold increase in the magnitude of the CTF band signal is not significantly different, being 0.27 nM for APP versus 0.24 nM for APLP1. This is the first example that a GSI can preferentially target APP processing while sparing other γ-substrates.

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Sala Frigerio, C., et al. 2009. Biochemistry48, 10894.
Kukar, TL., et al. 2008. Nature453, 925.

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Toxicity: Standard Handling (A)