LY2811376
Based on 13 publication(s) in Google Scholar
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.
- Purity: 99.62%
- CAS No.: 1194044-20-6
- Formula: C15H14F2N4S
- Molecular Weight:320.36
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) LY2811376
More- Transl Neurodegener. 2026 Jun 3;15(1):26. [Abstract]
- Genes Dis. 2020 Nov 21;8(6):867-881. [Abstract]
- Sci Adv. 2017 Feb 24;3(2):e1601068. [Abstract]
- J Agric Food Chem. 2022 Feb 9;70(5):1536-1546. [Abstract]
- ACS Omega. 2022 Aug 30;7(36):32131-32152. [Abstract]
- Stem Cells. 2017 Feb;35(2):374-385. [Abstract]
- FEBS J. 2017 Apr;284(7):1096-1109. [Abstract]
- Microb Pathog. 2025 Jul:204:107559. [Abstract]
- Bioorg Med Chem. 2018 Sep 15;26(17):4823-4840. [Abstract]
- Traffic. 2023 Jan;24(1):20-33. [Abstract]
- Res Sq. 2024 Jun 02.
- Research Square Preprint. 2023 Dec 1.
- University of Munich. 2018 Sep.
Customer Validation & Images
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WB
Biological Activity
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BACE1 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| H4 | IC50 |
0.27 μM
Compound: 1; LY2811376
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Inhibition of BACE1 in human H4 cells expressing APP751 Swedish mutant assessed as inhibition of amyloid beta 40 or amyloid beta 42 production incubated for 19 hrs by microplate reader analysis
Inhibition of BACE1 in human H4 cells expressing APP751 Swedish mutant assessed as inhibition of amyloid beta 40 or amyloid beta 42 production incubated for 19 hrs by microplate reader analysis
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[PMID: 26985314] |
| HEK293 | EC50 |
300 nM
Compound: 38, LY-2811376
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Inhibition of BACE1 in HEK293 cells expressing APPswedish mutant assessed as inhibition of amyloid beta production by ELISA
Inhibition of BACE1 in HEK293 cells expressing APPswedish mutant assessed as inhibition of amyloid beta production by ELISA
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[PMID: 24704031] |
| HEK293 | IC50 |
0.239 μM
Compound: 1; LY2811376
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Inhibition of human BACE1 (1 to 460 residues) expressed in HEK293 cells using mcaFRET peptide as substrate after 20 hrs by FRET assay
Inhibition of human BACE1 (1 to 460 residues) expressed in HEK293 cells using mcaFRET peptide as substrate after 20 hrs by FRET assay
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[PMID: 31786008] |
| HEK293 | IC50 |
0.24 μM
Compound: 1; LY2811376
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Inhibition of IgG1 Fc-fused human recombinant BACE1 (1 to 460 residues) expressed in HEK293 cells using methylcoumarin peptide harboring Swedish mutant as substrate incubated for 20 hrs by FRET assay
Inhibition of IgG1 Fc-fused human recombinant BACE1 (1 to 460 residues) expressed in HEK293 cells using methylcoumarin peptide harboring Swedish mutant as substrate incubated for 20 hrs by FRET assay
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[PMID: 26985314] |
| HEK293 | IC50 |
0.3 μM
Compound: 14
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Inhibition of BACE-1 in HEK293 cells expressing human APP751 cDNA harboring N670L671 mutation pretreated for 2 hrs followed by measuring after 2 hrs by sandwich ELISA
Inhibition of BACE-1 in HEK293 cells expressing human APP751 cDNA harboring N670L671 mutation pretreated for 2 hrs followed by measuring after 2 hrs by sandwich ELISA
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[PMID: 28749667] |
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1194044-20-6
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Appearance Solid
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Molecular Weight 320.36
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Formula C15H14F2N4S
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Color Off-white to yellow
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SMILES
FC1=C(C2=CN=CN=C2)C=C([C@]3(C)CCSC(N3)=N)C(F)=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (13)
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Journal Impact Factor
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Most Recent
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Transl Neurodegener
Persistent PirB cleavage drives Golgi-directed trafficking deficits underlying neurodegeneration. [Abstract]2026 Jun 3;15(1):26. PMID: 42231420 -
Genes Dis
2020 Nov 21;8(6):867-881. PMID: 34522714 -
Sci Adv
Differential contribution of APP metabolites to early cognitive deficits in a TgCRND8 mouse model of Alzheimer's disease. [Abstract]2017 Feb 24;3(2):e1601068. PMID: 28275722 -
J Agric Food Chem
Tangeretin Inhibits BACE1 Activity and Attenuates Cognitive Impairments in AD Model Mice. [Abstract]2022 Feb 9;70(5):1536-1546. PMID: 35084179 -
ACS Omega
Design, Synthesis, and Biological Evaluation of Notopterol Derivatives as Triple Inhibitors of AChE/BACE1/GSK3β for the Treatment of Alzheimer's Disease. [Abstract]2022 Aug 30;7(36):32131-32152. PMID: 36120034 -
Stem Cells
Depletion of the Fragile X Mental Retardation Protein in Embryonic Stem Cells Alters the Kinetics of Neurogenesis. [Abstract]2017 Feb;35(2):374-385. PMID: 27664080 -
FEBS J
2017 Apr;284(7):1096-1109. PMID: 28296235
LY2811376 purchased from MedChemExpress. Usage Cited in: FEBS J. 2017 Apr;284(7):1096-1109. [Abstract]
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.
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Microb Pathog
Actinobacillus pleuropneumoniae infection activates IL-1β expression in porcine alveolar macrophages via β-amyloid production. [Abstract]2025 Jul:204:107559. PMID: 40220800 -
Bioorg Med Chem
Novel multi-target compounds in the quest for new chemotherapies against Alzheimer's disease: An experimental and theoretical study. [Abstract]2018 Sep 15;26(17):4823-4840. PMID: 30181028 -
Traffic
AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice. [Abstract]2023 Jan;24(1):20-33. PMID: 36412210 -
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Solvent & Solubility
DMSO : ≥ 31 mg/mL (96.77 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (7.80 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (7.80 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (282 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
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. [Content Brief]
[2]. Zhang X, et al. Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer's disease. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9734-9. [Content Brief]
[3]. Ghosh AK, et al. Prospects of β-Secretase Inhibitors for the Treatment of Alzheimer's Disease. ChemMedChem. 2015 Sep;10(9):1463-6 [Content Brief]
[4]. Filser S, et al. Pharmacological inhibition of BACE1 impairs synaptic plasticity and cognitive functions. Biol Psychiatry. 2015 Apr 15;77(8):729-39. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 3.1215 mL | 15.6074 mL | 31.2149 mL | 78.0372 mL |
| 5 mM | 0.6243 mL | 3.1215 mL | 6.2430 mL | 15.6074 mL | |
| 10 mM | 0.3121 mL | 1.5607 mL | 3.1215 mL | 7.8037 mL | |
| 15 mM | 0.2081 mL | 1.0405 mL | 2.0810 mL | 5.2025 mL | |
| 20 mM | 0.1561 mL | 0.7804 mL | 1.5607 mL | 3.9019 mL | |
| 25 mM | 0.1249 mL | 0.6243 mL | 1.2486 mL | 3.1215 mL | |
| 30 mM | 0.1040 mL | 0.5202 mL | 1.0405 mL | 2.6012 mL | |
| 40 mM | 0.0780 mL | 0.3902 mL | 0.7804 mL | 1.9509 mL | |
| 50 mM | 0.0624 mL | 0.3121 mL | 0.6243 mL | 1.5607 mL | |
| 60 mM | 0.0520 mL | 0.2601 mL | 0.5202 mL | 1.3006 mL | |
| 80 mM | 0.0390 mL | 0.1951 mL | 0.3902 mL | 0.9755 mL |
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