Description General description A cell-permeable hydroxyethylene dipeptide isostere that acts as a highly specific and a potent inhibitor of γ-secretase (Aβtotal IC50 = 17 nM, Aβ40 IC50 = 48 nM, and Aβ42 IC50 = 67 nM in SHSY5Y cells overexpressing spβA4CTF). Binds to presenilin and blocks Notch intracellular domain production. Functions as a transition state analog mimic at the catalytic site of an aspartyl protease, however, it exhibits over 100-fold greater selectivity for γ-secretase than for cathepsin D. A cell-permeable hydroxyethylene dipeptide isostere that acts as a potent and highly specific inhibitor of γ-secretase (Aβ total IC50 = 17 nM; Aβ40 IC50 = 48 nM; and Aβ42 IC50 = 67 nM in SH-SY5Y cells overexpressing spβA4CTF). Binds to presenilin and blocks Notch intracellular domain production. Also reported to block the formation of εCTF, resulting in the accumulation of α- and βCTF. Functions as a transition state analog mimic at the catalytic site of an aspartyl protease, however, it exhibits over 100-fold greater selectivity for γ-secretase than for cathepsin D. Packaging 250, 500 μg in Plastic ampoule Biochem/physiol Actions Cell permeable: yes Primary Target Aβtotal Product does not compete with ATP. Reversible: no Target IC50: Aβtotal 17 nM, Aβ40 48 nM, and Aβ42 67 nM in SHSY5Y cells overexpressing spβA4CTF Packaging Packaged under inert gas Warning Toxicity: Standard Handling (A) Physical form A 1 mM (250 µg in 372 µl or 500 µg in 744 µl) solution in DMSO. Reconstitution Following initial thaw, aliquot and freeze (-20°C). Other Notes Weidemann, A., et al. 2002. Biochemistry41, 2825. Doerfler, P., et al. 2001. Proc. Natl. Acad. Sci. USA98, 9312. Li, Y.M., et al. 2000. Proc. Natl. Acad. Sci. USA97, 6138. Shearman, M.S., et al. 2000. Biochemistry39, 8698.