LY2811376

Catalog No.S1528

LY2811376 Chemical Structure

Molecular Weight(MW): 320.36

LY2811376 is the first orally available non-peptidic β-secretase(BACE1) inhibitor with IC50 of 239 nM-249 nM, that act to decrease Aβ secretion with EC50 of 300 nM, demonstrated to have 10-fold selectivity towards BACE1 over BACE2, and more than 50-fold inhibition over other aspartic proteases including cathepsin D, pepsin, or renin. Phase 1.

Size Price Stock Quantity  
In DMSO USD 220 In stock
USD 170 In stock
USD 320 In stock
USD 970 In stock
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Cited by 5 Publications

2 Customer Reviews

  • Neurobiol Aging 2014 35(7), 1570-81. LY2811376 purchased from Selleck.

    Representative immunofluorescence images of WT MEF cells (A and B) with a vector encoding APP. Cells were untreated or treated with 1 mm ascorbate for 1 h and stained with DAPI and mAb AM. Bar, 20 um. Exposure times were the same in all cases. Tg2576, MEFs from AD mouse model; DAPI, nuclear stain; A8717, antibody to C terminus of APP; Asc, ascorbate.

    J Biol Chem 2014 289(30), 20871-8. LY2811376 purchased from Selleck.

Purity & Quality Control

Choose Selective BACE Inhibitors

Biological Activity

Description LY2811376 is the first orally available non-peptidic β-secretase(BACE1) inhibitor with IC50 of 239 nM-249 nM, that act to decrease Aβ secretion with EC50 of 300 nM, demonstrated to have 10-fold selectivity towards BACE1 over BACE2, and more than 50-fold inhibition over other aspartic proteases including cathepsin D, pepsin, or renin. Phase 1.
Features Approximately 10-fold selectivity toward BACE1 over BACE2.
Targets
BACE1 [1] [1]
239 nM-249 nM ~300 nM(EC50)
In vitro

LY2811376 demonstrates concentration-dependent inhibition of hBACE1 with an IC50 of 239 and 249 nM against a small synthetic peptide or a larger chimeric protein substrate, respectively. LY2811376 treatment yields a concentration-dependent decrease in Aβ secretion in APP-overexpressing HEK293 cells. LY2811376 inhibits Aβ secretion with EC50 of ~100 nM in primary neuronal cultures of PDAPP transgenic mouse. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HEK293 cells NE\pbWdHfW6ldHnvckBie3OjeR?= NVfUfpJtUW6qaXLpeIlwdiCxZjDCRWNGOSCrbjDISWszQTNiY3XscJMh\XiycnXzd4lv\yCDUGDze4VlcXOqIH31eIFvfCCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKGGveXzvbYQh[mW2YTDwdo9lfWO2aX;uJIJ6KEWOSWPBMEBGSzVyPUCuN{DPxE1? NGe0[owzPDdyNECzNS=>

... Click to View More Cell Line Experimental Data

In vivo Administration of LY2811376 (10, 30, and 100 mg/kg doses) results in dose-dependent, significant reductions in Aβ, as well as sAPPβ and C99, the proximal cleavage products of APP proteolysis by BACE1 in APPV717F mouse model of Aβ pathology. After treatment with LY2811376 (5 mg/kg), reductions in Aβ1-x are observed in plasma, with a maximal 85% reduction observed from 4 to 12 h after dosing in beagle dogs. [1]

Protocol

Kinase Assay:

[2]

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Determination of enzymatic efficiency:

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 final concentration of at least 7 mg/mL. The optimal enzyme concentration for each FRET peptide substrate is determined individually at 30μM FRET peptide substrate in 50 mM ammonium acetate, pH 4.6, 1 mg/mL BSA and 1 mM Triton X-100. The enzymatic efficiency (kcat /Km) of either of the BACE1 orthologs toward individual FRET peptide substrates at 15, 30 and 100μM 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 fluorescence plate reader. Amino acid conjugated aminobenzoate is used to convert the emission signal in the relative fluorescence units into the molar concentration of product generated in the reaction mixture. The initial phase of the timedependence curve is fitted 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:

[1]

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  • Cell lines: APP-overexpressing HEK293.
  • Concentrations: ~ 100 μM
  • Incubation Time: 48–72 hours
  • Method:

    The cytotoxicity in the HEK293Swe cell model is assessed using a CellTiter 96 Aqueous Non-Radioactive Cell Proliferation Assay.


    (Only for Reference)
Animal Research:

[1]

+ Expand
  • Animal Models: PDAPP transgenic mice.
  • Formulation: In 7% Pharmasolve
  • Dosages: 10, 30, and 100 mg/kg doses
  • Administration: P.O.
    (Only for Reference)

Solubility (25°C)

In vitro Ethanol 64 mg/mL (199.77 mM)
DMSO 16 mg/mL (49.94 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 320.36
Formula

C15H14F2N4S

CAS No. 1194044-20-6
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00838084 Completed Alzheimer''s Disease Eli Lilly and Company December 2008 Phase 1
NCT00838084 Completed Alzheimer''s Disease Eli Lilly and Company December 2008 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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BACE Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID