AChE/Nrf2 modulator 1

AChE/Nrf2 modulator 1 is an orally active acetylcholinesterase (AChE)/nuclear factor erythroid 2-related factor 2 (Nrf2) modulator. AChE/Nrf2 modulator 1 has Nrf2 inductive activity and AChE inhibitory activity for eeAChE and hAChE with IC50 values of 0.07 μM and 0.38 μM, respectively. AChE/Nrf2 modulator 1 can be used for the research of Alzheimer's disease[1].

Signaling Pathways >> NF-κB >> Keap1-Nrf2

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> AChE

IC50: 0.07 μM (eAChE); 0.38 μM (hAChE)[1]

AChE/Nrf2 modulator 1 (Compound 15a) 具有显着的 Nrf2 诱导性， 对 eeAChE 和 hAChE 具有出色的 AChE 抑制作用，IC50 值分别为 0.07 μM 和 0.38 μM[1]。 AChE/Nrf2 modulator 1 (5, 20 μM; 5-12 h) 上调 Nrf2 及其下游蛋白 HO1、NQO1 和 GCLM 的蛋白和转录水平，促进 Nrf2 从细胞质转运到细胞核[1]。 AChE/Nrf2 modulator 1 (1, 2.5, 5, 10, 20, 40 μM) 在保护细胞免受 H2O2 和 Aβ1-42 聚集的损害方面表现出重要的神经保护功能，发挥抗氧化应激和抗炎活性，减少 ROS 和促炎细胞因子的产生[1]。 Western Blot Analysis[1] Cell Line: PC12 cells Concentration: 20 μM; 5, 20 μM Incubation Time: 5-10 h; 6 h Result: Significantly activated the expression of Nrf2 downstream proteins. Increase the level of Nrf2 and its downstream protein HO-1, NQO1, and GCLM in a dose-dependent manner at 6 h. Increased the translocation of Nrf2 into the nucleus. RT-PCR[1] Cell Line: PC12 cells Concentration: 20 μM Incubation Time: 0, 1, 2, 5, 10, 24 h Result: Increased the Nrf2, HO-1, NQO1, and GCLM gene expression in dose dependent manner. Immunofluorescence[1] Cell Line: PC12 cells Concentration: 5, 20 μM Incubation Time: 12 h Result: Induced the Nrf2 translocation into the nucleus in dose dependent manner.

AChE/Nrf2 modulator 1 (Compound 15a) (口服；10 mg/kg；连续10天) 有效缩短了潜伏期和逃逸到目标的距离，增加了到达时间，并简化了由 scopolamine 和 Aβ1-42 诱导的 Morris 水迷宫试验中的轨迹[1]。 AChE/Nrf2 modulator 1 可显着降低小鼠模型大脑中促炎因子的水平[1]。 Animal Model: ICR mice[1] Dosage: 10, 20 mg/kg Administration: Intragastric administration; oral; for 10 consecutive days Result: Significantly reduced the latency time to target and simplified the traveled distance and exhibited a good effect on ameliorating ethological changes and spatial memory impairment by rescuing cholinergic function .Showed an obvious reduction of pro-inflammation factors level and significantly increased the content of TGF-β1.

[1]. Yuanyuan Wang, et al. Design, synthesis and evaluation of fused hybrids with acetylcholinesterase inhibiting and Nrf2 activating functions for Alzheimer's disease. Eur J Med Chem. 2022 Dec 15;244:114806.