γ-Secretase Inhibitor X

Cell permeable: yes

Primary Target
Aβ_total

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

Toxicity: Standard Handling (A)

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.

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.

Packaged under inert gas

A 1 mM (250 µg in 372 µl or 500 µg in 744 µl) solution in DMSO.

Following initial thaw, aliquot and freeze (-20°C).

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