1. Neuronal Signaling
  2. Beta-secretase

LY2811376 

Cat. No.: HY-10472 Purity: 99.67%
Data Sheet SDS Handling Instructions

LY2811376 is the first orally available non-peptidic β-secretase (BACE1) inhibitor with IC50 of 239 nM-249 nM, that acts to decrease Aβ secretion with EC50 of 300 nM, and demonstrates 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.

For research use only. We do not sell to patients.
LY2811376 Chemical Structure

LY2811376 Chemical Structure

CAS No. : 1194044-20-6

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $132 In-stock
5 mg $120 In-stock
10 mg $200 In-stock
50 mg $580 In-stock
100 mg $900 In-stock
200 mg   Get quote  
500 mg   Get quote  

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    LY2811376 purchased from MCE. Usage Cited in: FEBS J. 2017 Apr;284(7):1096-1109.

    SH-SY5Y cells are transfected with APPsw plasmid together with ciRS-7 plasmid or control plasmids for 48 h, then the transfected cells are treated with 100 μM BI LY2811376, or 20 μM TAPI or DMSO as vehicle control for an additional 12 h. Cell lysates are analyzed by 12% Tris/Tricine gel with C20 antibody to detect APP C-terminal fragments C99 and C83, 10% Tris/Tricine gel to detect full-length APP and NRG.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    LY2811376 is the first orally available non-peptidic β-secretase (BACE1) inhibitor with IC50 of 239 nM-249 nM, that acts to decrease Aβ secretion with EC50 of 300 nM, and demonstrates 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.

    IC50 & Target

    IC50: 239-249 nM (BACE1)

    In Vitro

    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 EC50 of 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].

    In Vivo

    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 Aβ1-40 PD 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].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 3.1215 mL 15.6074 mL 31.2149 mL
    5 mM 0.6243 mL 3.1215 mL 6.2430 mL
    10 mM 0.3121 mL 1.5607 mL 3.1215 mL
    Please refer to the solubility information to select the appropriate solvent.
    Animal Administration
    [1]

    LY2811376 is formulated in 1% (w/v) hydroxyethylcellulose, 0.25% (v/v) polysorbate 80, and 0.05% (v/v) Dow Corning Antifoam 1510-US in reverse osmosis water.

    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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    320.36

    Formula

    C₁₅H₁₄F₂N₄S

    CAS No.

    1194044-20-6

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 31 mg/mL

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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    LY2811376
    Cat. No.:
    HY-10472
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