LY2811376 is the first orally available non-peptidic BACE1 inhibitor that produces profound Aβ-lowering effects in animals. LY2811376 has 10-fold selectivity towards BACE1 over BACE2, and more than 50-fold inhibition over other aspartic proteases including cathepsin D, pepsin, or renin. LY2811376 inhibits Aβ secretion with EC50 of ~100 nM in primary neuronal cultures of PDAPP transgenic mouse. Administration of LY2811376 (10, 30 and 100 mg/kg doses) results in dose-dependent, significant reductions in Aβ, as well as sAPPβ and C99. LY2811376 treatment yields a concentration-dependent decrease in Aβ secretion in APP-overexpressing HEK293 cells.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||Ethanol 50 mg/mL|
Validation of a multiplex assay for simultaneous quantification of amyloid-β peptide species in human plasma with utility for measurements in studies of Alzheimer's disease therapeutics.
Lachno DR, et al. J Alzheimers Dis. 2012;32(4):905-18. PMID: 22886018.
Robust central reduction of amyloid-β in humans with an orally available, non-peptidic β-secretase inhibitor.
May PC, et al. J Neurosci. 2011 Nov 16;31(46):16507-16. PMID: 22090477.
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