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.
LY2811376 细胞实验
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.
Alzheimers Res Ther. 2014 Nov 17;6(5-8):75.
HEK-293 cells
260 nM
As a positive control, LY2811376 showed an IC50 value of 260 nM, indicating inhibitory activity against BACE1
Chem Sci. 2016 Oct 19;7(10):6563-6572.
LY2811376 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
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
EMBO J. 2013 Jul 17;32(14):2015-28
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
Chem Sci. 2016 Oct 19;7(10):6563-6572.
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
Mol Imaging Biol. 2019 Feb;21(1):35-43
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
Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9734-9
United States, California
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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 收起 <<
United States, California
... 展开 >>
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 收起 <<
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