LY2811376 is a non-peptidic inhibitor of BACE1.
Beta-secretase 1 (BACE1) is an aspartic-acid protease that cleaves the amyloid precursor protein (APP) into amyloid-βpeptide (Aβ), which plays a critical role in Alzheimer's disease (AD).
In recombinant enzyme assays, LY2811376 inhibited hBACE1 with IC50 values of 249 nM and 239 nM against a larger chimeric protein substrate and a small synthetic peptide, respectively. In a human embryonic kidney cell line overexpressed APP, LY2811376 decreased Aβ secretion with EC50 value of 300 nM in a concentration-dependant way [1]. In SH-SY5Y cells, LY2811376 reduced Aβ1-40 and Aβ1-42 secreted to the cell medium while increased the level of Aβ5-40 [2].
In the APPV717F mouse, LY2811376 significantly reduced Aβ, as well as sAPP and C99, the cleavage products of APP by BACE1 [1]. In a healthy population (n =18), LY2811376 (30 mg, 90 mg) increased Aβ5-40 and Aβ5-X in a dose-dependant way, while Aβ1-34 reduced in a same way. These results suggested that LY2811376 inhibited N-terminally truncated Aβ peptides in a BACE1-independent pathway [2].
References:
[1]. May PC, Dean RA, Lowe SL, et al. Robust Central Reduction of Amyloid- in Humans with an
Orally Available, Non-Peptidic -Secretase Inhibitor. J Neurosci, 2011, 31(46): 16507-16516.
[2]. Portelius E, Dean RA, Andreasson U, et al. β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) inhibitor treatment induces Aβ5-X peptides through alternative amyloid precursor protein cleavage. Alzheimers Res Ther, 2014, 6(5-8): 75.
LY2811376
| 规格 | 价格 | 库存 | 数量 | 操作 |
|---|---|---|---|---|
| 1mg | ¥512.00 | 现货 | 1 | |
| 5mg | ¥1,127.00 | 现货 | 1 | |
| 10mg | ¥1,800.00 | 现货 | 1 | |
| 25mg | ¥3,240.00 | 现货 | 1 | |
| 50mg | ¥5,040.00 | 现货 | 1 | |
| 10mM (in 1mL DMSO) | ¥794.00 | 现货 | 1 |
文献被引
本产品暂无引用记录;以下为 GlpBio 产品在 Nature / Cell / Science 等顶刊的客户引用样例
Nature641, 529–536 (2025)
Nature628, 630–638 (2024)
Nature632, 686–694 (2024)
Nature618, 1017–1023 (2023)
Nature610, 366–372 (2022)
Cell187(9):2288-2304 (2024)
Cell183(7):1867-1883 (2020)
Science388(6745) (2025)
Science387(6739) (2025)
Science387(6734) (2025)
Cell Research35, 97–116 (2025)
Cell Research34, 683–706 (2024)
Cell Research33, 273–287 (2023)
Cell Research33, 546–561 (2023)
Cell Research33, 904–922 (2023)
Cell Research31, 1291–1307 (2021)
产品描述 Description
实验参考方法 Experimental Reference Method
Animal experiment: | Sprague Dawley [Crl:CD(SD)] rats (10 per sex per group), appr 7 weeks of age, are given 0 (vehicle only), 10, 30, or 100 mg/kg LY2811376 by daily oral gavage. Vehicle consists of 1% (w/v) hydroxyethylcellulose, 0.25% (v/v) polysorbate 80, and 0.05% (v/v) Dow Corning Antifoam 1510-US in reverse osmosis water. At necropsy after 3 months of treatment, tissues are immersion fixed in 10% neutral-buffered formalin (brain) or modified Davidson's solution (eyes) and then processed by routine methods to paraffin block and hematoxylin-eosin (H&E)-stained histologic slides. From selected animals given 100 mg/kg on a subsequent investigative study, eyes are fixed in modified Karnovsky's solution, processed routinely into epoxy resin, and then ultrathin sections stained with uranyl acetate and Sato's lead citrate are examined in a transmission electron microscope. In a separate study, BACE1 knock-out mice (B6.129-Bace1tm1Pcw/J) are given 0 or 100 mg/kg LY2811376 by daily oral gavage for 9 weeks, and then necropsied tissues are collected and examined by light microscopy as described above for the rat toxicology study. |
References: [1]. May PC, et al. Robust central reduction of amyloid-β in humans with an orally available, non-peptidic β-secretase inhibitor. J Neurosci. 2011 Nov 16;31(46):16507-16516. |
产品文档 Product Documents
化学性质Chemical Properties
储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
为了提高溶解度，请将管子加热至 37°C，然后在超声波浴中震荡一段时间。