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Catalog No. T2639Cas No. 1194044-20-6
LY2811376, an orally available non-peptidic β-secretase(BACE1) inhibitor (IC50: 239-249 nM), can decrease Aβ secretion (EC50: 300 nM). It has 10-fold selectivity towards BACE1 over BACE2, and more than 50-fold inhibition over other aspartic proteases including pepsin, cathepsin D, or renin.
All TargetMol products are for research purposes only and cannot be used for human consumption. We do not provide products or services to individuals. Please comply with the intended use and do not use TargetMol products for any other purpose.
Pack SizePrice/USDAvailabilityQuantity
1 mg$48In Stock
2 mg$67In Stock
5 mg$125In Stock
10 mg$216In Stock
25 mg$393In Stock
50 mg$589In Stock
100 mg$843In Stock
1 mL x 10 mM (in DMSO)$125In Stock
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Product Introduction

LY2811376, an orally available non-peptidic β-secretase(BACE1) inhibitor (IC50: 239-249 nM), can decrease Aβ secretion (EC50: 300 nM). It has 10-fold selectivity towards BACE1 over BACE2, and more than 50-fold inhibition over other aspartic proteases including pepsin, cathepsin D, or renin.
In vitro
In the APPV717F mouse model of Aβ pathology, LY2811376 (10/30/100 mg/kg) induced a dose-dependent significant reduction in Aβ, sAPPβ, and C99, which are the closest breakdown products following the hydrolysis of APP by BACE1 protein. In beagle dogs, LY2811376 (5 mg/kg) resulted in a decrease in plasma Aβ1-x levels, with the maximum reduction of 85% occurring between 4-12 hours post-administration.
In vivo
LY2811376 exhibits a concentration-dependent reduction in the secretion of Aβ in HEK293 cells overexpressing APP. It also concentration-dependently inhibits hBACE1, including small synthetic peptide substrates (IC50: 239 nM) and larger chimeric protein substrates (IC50: 249 nM). In primary neuronal cultures from PDAPP transgenic mice, LY2811376 inhibits Aβ secretion (EC50: 100 nM).
Kinase Assay
Determination of enzymatic ef?ciency: The stock solution for each FRET peptide substrate is prepared at 30 mM in dimethylsulfoxide (DMSO). The huBACE1:Fc muBACE1:Fc preparation is concentrated through YM10 Centricon. to a ?nal concentration of at least 7 mg/mL. The optimal enzyme concentration for each FRET peptide substrate is determined individually at 30 μM FRET peptide substrate in 50 mM ammonium acetate, pH 4.6, 1 mg/mL BSA and 1 mM Triton X-100. The enzymatic ef?ciency (kcat /Km) of either of the BACE1 orthologs toward individual FRET peptide substrates at 15, 30 and 100 μM is determined under the optimal conditions for each substrate. The progress of the reaction is monitored by measuring an increase of the emission signal at 420 nm with excitation wavelength set at 320 nm, using a GEMINI ?uorescence plate reader. Amino acid conjugated aminobenzoate is used to convert the emission signal in the relative ?uorescence units into the molar concentration of product generated in the reaction mixture. The initial phase of the timedependence curve is ?tted with a linear function whose slope is used to calculate the initial rate for huBACE1:Fc toward each peptide substrate. The kcat /Km values are calculated from the linear dependence of the initial rate on the concentration of each peptide.
Cell Research
The cytotoxicity in the HEK293Swe cell model is assessed using a CellTiter 96 Aqueous Non-Radioactive Cell Proliferation Assay. (Only for Reference)
Chemical Properties
Molecular Weight320.36
Cas No.1194044-20-6
Storage & Solubility Information
StoragePowder: -20°C for 3 years | In solvent: -80°C for 1 year
Solubility Information
H2O: < 1 mg/mL (insoluble or slightly soluble)
DMSO: 13 mg/mL (40.6 mM)
Ethanol: 60 mg/mL (187.3 mM)
Solution Preparation Table
1 mM3.1215 mL15.6074 mL31.2149 mL156.0744 mL
5 mM0.6243 mL3.1215 mL6.2430 mL31.2149 mL
10 mM0.3121 mL1.5607 mL3.1215 mL15.6074 mL
20 mM0.1561 mL0.7804 mL1.5607 mL7.8037 mL
50 mM0.0624 mL0.3121 mL0.6243 mL3.1215 mL
100 mM0.0312 mL0.1561 mL0.3121 mL1.5607 mL


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