LY2811376 is the first orally available non-peptidicβ-secretase (BACE1)inhibitor withIC₅₀of 239 nM-249 nM, that acts to decrease Aβ secretion withEC₅₀of 300 nM, and demonstrates to have 10-fold selectivity towardsBACE1overBACE2, and more than 50-fold inhibition over other aspartic proteases includingcathepsin D, pepsin, orrenin.

IC50: 239-249 nM (BACE1)

In an APP-overexpressing human embryonic kidney cell line, LY2811376 treatment yields a concentration-dependent decrease in Aβ secretion with a half-maximal effective concentration (EC₅₀) of appr 300 nM. LY2811376 treatment of primary neuronal cultures of PDAPP transgenic mouse produces a concentration-dependent decrease in Aβ secretion with an EC₅₀of appr 100 nM^[1]. LY2811376 has good ADME properties (BACE1 IC₅₀=240 nM, cellular potency IC₅₀=300 nM) and selectivity (BACE2 and cathepsin D selectivity: appr 10- and 65-fold, respectively)^[3]. LY2811376 reduces the Aβ40 levels in cortex and plasma without change of health and weight in a dose-dependent manner^[4].

LY2811376 (10, 30, and 100 mg/kg, p.o.) results in dose-dependent, significant reductions in Aβ as well as sAPPβ and C99, the proximal cleavage products of APP proteolysis by BACE1. LY2811376 produces dose-dependent decreases in all APP-related PD markers of BACE1 inhibition in PDAPP mice. Low (30 mg) and high (90 mg) doses of LY2811376 investigated in the CSF sampling study are based on PK and plasma Aβ^1-40PD observed in the SAD study^[1]. LY2811376 (30 mg/kg, p.o.) can lead to a 60% decrease in the soluble Aβs in mouse cortex^[2]. LY2811376 (100 mg/kg, p.o.) decreases the spine density and formation in mice. LY2811376 (100 mg/kg every 12 hours over 16 days) causes a reduction in the frequency of sEPSC and mEPSC, whereas the effects of LY2811376 on the amplitude of sEPSC fails to reach significance^[4].

320.36

Solid

C₁₅H₁₄F₂N₄S

1194044-20-6

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 31 mg/mL(96.77 mM)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (7.80 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.80 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 2.5 mg/mL (7.80 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.80 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (7.80 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (7.80 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。