产品说明书

	同义名 :	LY2886721 hydrochloride
	CAS号 :	1262036-49-6
	货号 :	A1226355
	分子式 :	C18H17ClF2N4O2S
	纯度 :	99%+
	分子量 :	426.868
	MDL号 :	MFCD24387533
	存储条件：	粉末 Inert atmosphere,2-8°C 液体 -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性
描述	BACE1, also known as β-secretase, is an aspartyl protease that controls the formation of amyloid β, a peptide crucial for the pathogenesis of Alzheimer’s disease. LY2886721 is a potent BACE1 inhibitor with an IC50 value of 20.3±10.1nM. It also exhibits inhibitory activity against human BACE2, a closely related aspartyl protease, with an IC50 value of 10.2±4.8nM. Overnight treatment of HEK293Swe cells with increasing concentrations of LY2886721 led to a dose-dependent decrease in the amount of amyloid β secreted into the medium. The EC50 values for the inhibition of amyloid β1-40 and amyloid β1-42 were 18.5nM and 19.7nM, respectively. Overnight exposure of mouse neuronal cultures with increasing concentrations of LY2886721 also dose-dependently decreased the production of amyloid β with an EC50 value of ~10nM. In PDAPP mice, oral administration of LY2886721 at 3, 10, and 30mg/kg significantly reduced hippocampal and cortical levels of amyloid β1-x compared with the vehicle-treated group. Mice administered with LY2886721 showed reduced brain parenchymal levels of C99 (at 10 and 30mg/kg) and sAPPβ (at 3, 10, and 30mg/kg) compared to the control group.[1]
作用机制	LY2886721 is a BACE1 active site inhibitor with selectivity against cathepsin D, pepsin, and renin.[1]

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.34mL 0.47mL 0.23mL	11.71mL 2.34mL 1.17mL	23.43mL 4.69mL 2.34mL

参考文献

[1]May PC, Willis BA, Lowe SL, Dean RA, Monk SA, Cocke PJ, Audia JE, Boggs LN, Borders AR, Brier RA, Calligaro DO, Day TA, Ereshefsky L, Erickson JA, Gevorkyan H, Gonzales CR, James DE, Jhee SS, Komjathy SF, Li L, Lindstrom TD, Mathes BM, Martényi F, Sheehan SM, Stout SL, Timm DE, Vaught GM, Watson BM, Winneroski LL, Yang Z, Mergott DJ. The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans. J Neurosci. 2015 Jan 21;35(3):1199-210. doi: 10.1523/JNEUROSCI.4129-14.2015