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Chemical Structure| 1194044-20-6 Chemical Structure| 1194044-20-6

Structure of LY2811376
CAS No.: 1194044-20-6

Chemical Structure| 1194044-20-6

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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.

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Product Details of LY2811376

CAS No. :1194044-20-6
Formula : C15H14F2N4S
M.W : 320.36
SMILES Code : NC1=N[C@](C)(C2=CC(C3=CN=CN=C3)=C(F)C=C2F)CCS1
MDL No. :MFCD18074525
InChI Key :MJQMRGWYPNIERM-HNNXBMFYSA-N
Pubchem ID :44251605

Safety of LY2811376

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
SH-SY5Y cells 1.25 μM and 2.5 μM 20 hours To evaluate the inhibitory effect of LY2811376 on BACE1, results showed that LY2811376-treated cells secreted less Aβ1-40 and Aβ1-42, while the relative levels of Aβ5-40 increased. PMC4233234
HEK-293 cells 260 nM As a positive control, LY2811376 showed an IC50 value of 260 nM, indicating inhibitory activity against BACE1 PMC5131395

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice APP/PS1 transgenic mice Oral 30 mg/kg Single dose To monitor the rapid reduction of soluble Aβ in APP/PS1 mice by LY2811376, results showed a 33% decrease in fluorescence signal after treatment PMC4534214
Mice 3xTg AD mouse model intracerebroventricular injection 2 mg/mL single dose 48 hours before the task LY2811376 exhibited activity similar to that of compound 1 in the 3xTg AD mouse model, improving learning and memory deficits PMC5131395
Mice Bace1 mutant mice Oral 100 mg/kg/day Once daily for 29 days To evaluate the effect of Bace1 inhibitor Ly2811376 on muscle spindle maintenance and motor coordination in adult mice, results showed that long-term inhibition of Bace1 leads to a reduction in muscle spindle numbers and impaired motor coordination PMC3715864
Mice APP/PS1 transgenic mice Intravenous injection 2.5 mg/ml Continuous 3 days Monitor the therapeutic effects of LY2811376, results showed a 70% reduction in NIRFOI signal in APP/PS1 mice after treatment PMC7673911

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00838084 Alzheimer's Disease Phase 1 Completed - United States, California ... More >> For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Glendale, California, United States Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.12mL

0.62mL

0.31mL

15.61mL

3.12mL

1.56mL

31.21mL

6.24mL

3.12mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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