Description General description A cell-permeable, potent, selective, peptidomimetic, non-transition-state analog inhibitor of γ-secretase and Notch processing (IC50 = 300 pM for Aβ40 in CHO cells overexpressing wild type βAPP; 240 pM for Aβ40, 370 pM for Aβ42, and 320 pM for NICD, respectively, in HEK293 cells stably transfected with βAPP695 and mNotchΔE(M1727V); 100 pM for both Aβ40 and Aβ42 in SH-SY5Y cells stably transfected with SPA4CT). Lowers Aβ levels in several APP transgenic mouse models. Reported to bind to presenilins and suppress the proteolytic cleavage of transmembrane protein substrates, including APLP1 and APLP2, CD44, ErbB4, E-cadherin, low density lipoprotein receptor-related proteins, Notch ligands, and p75NTR. Only weakly affects presenilinase activity at much higher concentrations (200-400 µM). Packaging 1 mg in Glass bottle 500 μg in Plastic ampoule Biochem/physiol Actions Cell permeable: yes Primary Target γ-secretase and Notch processing Ab40 in CHO cells overexpressing wild type bAPP Product does not compete with ATP. Reversible: no Target IC50: 300 pM for Aβ40 in CHO cells overexpressing wild typeβAPP; 240 pM for Aβ40, 370 pM for Aβ42, and 320 pM for NICD, respectively, in HEK293 cells stably transfected with βAPP695 and mNotchΔE(M1727V); 100 pM for both Aβ40 Packaging Packaged under inert gas Warning Toxicity: Standard Handling (A) Reconstitution Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C. Other Notes Milano, J., et al. 2004. Toxicol. Sci.82, 341. Jung, K.M., et al. 2003. J. Biol. Chem.278, 42161. Murakami, D., et al. 2003. Oncogene22, 1511. Campbell, W.A., et al. 2003. J. Neurochem.85, 1563. Berechid, B.E., et al., 2002. J. Biol. Chem.277, 8154. Lee, H.J., et al. 2002. J. Biol. Chem.277, 6318. May, P., et al. 2002. J. Biol. Chem.277, 18736. Scheinfeld, M.H., et al. 2002. J. Biol. Chem.277, 44195. Ni, C. Y., et al. 2001. Science294, 2179. Beher, D., et al. 2001. J. Biol. Chem.276, 45394. Doerfler, P., et al. 2001. Proc. Natl. Acad. Sci. USA98, 9312. Seiffert, D., et al. 2000. J. Biol. Chem.275, 34086.