| Description | 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 | 体外研究用以探讨E2012对胆固醇代谢的影响表明，E2012在胆固醇生物合成的最后阶段抑制了3β-羟甾 Δ24-还原酶(DHCR24)[1]。 |
| In vivo | 9只犬分别接受了单剂量的γ-分泌酶调节剂E 2012、γ-分泌酶抑制剂LY450139或对照剂的处理，给药间隔为1周。通过免疫沉淀结合MALDI-TOF质谱分析了CSF Aβ同型体模式。处理后，Aβ(1-15)和Aβ(1-16)水平升高，而Aβ(1-34)水平下降，这与之前关于γ-分泌酶抑制剂LY450139的研究结果一致。E 2012处理以剂量依赖性方式显著增加了Aβ(1-37)的水平，同时Aβ(1-39)、Aβ(1-40)和Aβ(1-42)的水平下降。这些数据表明，γ-分泌酶调节剂E 2012更改了γ-分泌酶的切割位点偏好。Aβ(1-37)的增加可能会抑制Aβ(1-42)的寡聚化和毒性。 |
| Synonyms | (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 |
| molecular weight | 419.49 |
| Molecular formula | C25H26FN3O2 |
| CAS | 870843-42-8 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 50 mg/mL (119.19 mM) |
| References | 1. Nakano-Ito K, et al. E2012-induced cataract and its predictive biomarkers. Toxicol Sci. 2014 Jan;137(1):249-58. 2. Portelius E, Van Broeck B, Andreasson U, Gustavsson MK, Mercken M, Zetterberg H, Borghys H, Blennow K.Acute effect on the Aβ isoform pattern in CSF in response to γ-secretase modulator and inhibitor treatment in dogs.J Alzheimers Dis. 2010;21(3):1005-12. |