Biochem/physiol Actions

Primary TargetAβ_total

Reversible: no

Product does not compete with ATP.

Target IC₅₀: Aβtotal 17 nM, Aβ40 48 nM, and Aβ42 67 nM in SHSY5Y cells overexpressing spβA4CTF

Cell permeable: yes

General description

A cell-permeable hydroxyethylene dipeptide isostere that acts as a highly specific and a potent inhibitor of γ-secretase (Aβ_total 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.

Legal Information

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

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.

Packaging

250, 500 µg in Plastic ampoule

Packaged under inert gas

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).

Warning

Toxicity: Standard Handling (A)