Biochem/physiol Actions

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

Primary Targetγ-secretase and Notch processing Ab40 in CHO cells overexpressing wild type bAPP

Product does not compete with ATP.

Cell permeable: yes

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 p75^NTR. Only weakly affects presenilinase activity at much higher concentrations (200-400 µM).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

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.

Packaging

Packaged under inert gas

1 mg in Glass bottle

500 µg in Plastic ampoule

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Warning

Toxicity: Standard Handling (A)