Sulindac Sulfide

Sulindac sulfide is a noncompetitive γ-secretase inhibitor, with an IC50 of 20.2 μM for γ42-secretase activity.

Signaling Pathways >> Neuronal Signaling >> γ-secretase

Signaling Pathways >> Stem Cell/Wnt >> γ-secretase

Research Areas >> Neurological Disease

IC50: 20.2 μM (γ42-secretase)[1].

Treatment with 100 μM of Sulindac sulfide (SSide) causes cell death presumably by inducing apoptosis, resulting in marked decrease in Aβgeneration as well as in total protein expression. The IC50 value for Aβ42 secretion of Sulindac sulfide is 30.6±2.8 μM. SSone and naproxen have no effect either on Aβ40 or Aβ42 secretion as well as on Notch cleavage up to 100 μM. It is observed that an inhibition of γ42-secretase activity by Sulindac sulfide in a dose-dependent manner. The IC50 value of SSide for inhibiting γ42-secretase activity in vitro is 20.2±2.6 μM. A decrease is found in slope by the increase of the concentration of SSide in the plot of rate against the enzyme concentration, suggesting that Sulindac sulfide is not an irreversible or pseudo-irreversible inhibitor. Moreover, when the dialyzed solubilizedγ-secretase fraction is pretreated with Sulindac sulfide against CHAPSO buffer without Sulindac sulfide, γ-secretase activity is almost totally recovered. From these data, it is strongly suggested that the genuine molecular target of Sulindac sulfide is the γ-secretase complex and that Sulindac sulfide works as a reversible γ-secretase inhibitor[1].

[1]. Takahashi Y, et al. Sulindac sulfide is a noncompetitive gamma-secretase inhibitor that preferentially reduces Abeta 42 generation. J Biol Chem. 2003 May 16;278(20):18664-70.

DAPT (GSI-IX) | RO4929097 | YO-01027 | PF-3084014 | LY-411575 | L-685,458 | MK-0752 | Avagacestat | Semagacestat(LY450139) | Z-Ile-Leu-aldehyde | E 2012 | gamma-secretase modulator 1 | NGP555 | BMS 299897 | gamma-secretase modulator 3