LY2886721 

LY2886721 is a potent, selective and orally active beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor with an IC₅₀ of 20.3 nM for recombinant human BACE1. LY2886721 is selectivity against cathepsin D, pepsin, and renin, but lacking selectivity against BACE2 (IC₅₀ of 10.2 nM). LY2886721 can across blood-brain barrier and has the potential for Alzheimer's disease treatment^[1].

IC50: 20.3 nM (Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1)); 10.2 nM (BACE2)^[1]

Overnight exposure of HEK293Swe cells to increasing concentrations of LY2886721 shows a concentration-dependent decrease in the amount of Aβ secreted into the condition medium. Consistent with a mechanism of BACE inhibition, the EC₅₀s for inhibition of Aβ_1-40 and Aβ_1-42 are essentially identical, 18.5 and 19.7 nM, respectively^[1].
Overnight exposure of PDAPP neuronal cultures to an increasing concentration of LY2886721 produces a concentration-dependent decrease in Aβ production. As observed in HEK293Swe cells, the EC₅₀s for inhibition of Aβ_1-40 and Aβ_1-42 are comparable in PDAPP neuronal cultures at ∼10 nM^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

LY2886721 (3-30 mg/kg; oral administration; PDAPP mice) treatment significantly reduces the hippocampal and cortical levels of Aβ_1-x. LY2886721 treatment results in significant reduction of brain parenchymal levels of C99 and sAPPβ^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

390.41

Solid

C₁₈H₁₆F₂N₄O₂S

1262036-50-9

FC1=CN=C(C=C1)C(NC2=CC=C(C([C@@]34[C@]([H])(CSC(N)=N4)COC3)=C2)F)=O

Room temperature in continental US; may vary elsewhere.

• [1]. May PC1, et al. 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.  [Content Brief]