E 2012 是一种γ 分泌酶调节剂，不会影响 Notch 加工，在胆固醇生物合成的最后一步抑制 3β-羟基固醇 Δ24-还原酶。它能够减少淀粉样蛋白 β-42 减少阿兹海默氏病，并在大鼠多次重复给药后诱发白内障。

E2012 is a γ-secretase modulator (GSM). E2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final step in the cholesterol biosynthesis. E 2012 aims at Alzheimer's disease by reduction of amyloid β-42, and induces cataract following repeated doses in the rat.

In vitro studies to investigate the effect of E2012 on cholesterol metabolism demonstrated that E2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final step in the cholesterol biosynthesis[1].

9 dogs were treated with a single dose of the γ-secretase modulator E2012, the γ-secretase inhibitor LY450139, or vehicle with a dosing interval of 1 week.?The CSF Aβ isoform pattern was analyzed by immunoprecipitation combined with MALDI-TOF mass spectrometry.?Aβ(1-15) and Aβ(1-16) increase while Aβ(1-34) decreases in response to treatment with the γ-secretase inhibitor LY450139, which is in agreement with previous studies.?The isoform Aβ(1-37) was significantly increased in a dose-dependent manner in response to treatment with E2012, while Aβ(1-39), Aβ(1-40) and A(1-42) decreased.?The data presented suggests that the γ-secretase modulator E-2012 alters the cleavage site preference of γ-secretase.?The increase in Aβ(1-37) may inhibit Aβ(1-42) oligomerization and toxicity[2].

870843-42-8

C25H26FN3O2

419.49

(E)-1-[(1S)-1-(4-氟苯基)乙基]-3-[3-甲氧基-4-(4-甲基-1H-咪唑-1-YL)亚苄基]哌啶-2-酮

DMSO:50 mg/mL (119.19 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years