LY2886721

Research use only, not for human use.

LY2886721 is a highly potent, selective BACE1 aspartyl protease inhibitor with IC50 of 20.3 and 10.2 nM for BACE1 and BACE2.

LY2886721 is a highly potent, selective BACE1 aspartyl protease inhibitor with IC50 of 20.3 and 10.2 nM for BACE1 and BACE2, shows no inhibition against cathepsin D, pepsin, renin, or other aspartyl proteases; produces a concentration-dependent decrease in Aβ1-40 and Aβ1-42 production in HEK293Swe cells (EC50s=10 nM); demonstrates robust in vivo amyloid β lowering effect in nonclinical animal models, shows similar potent and persistent amyloid β lowering was observed in plasma and lumbar in clinical trials.Alzheimer Disease Phase 2 Discontinued(In Vitro):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 Aβ1-40 and Aβ1-42 are essentially identical, 18.5 and 19.7 nM, respectively.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 Aβ1-40 and Aβ1-42 are comparable in PDAPP neuronal cultures at ～10 nM. (In Vivo):LY2886721 (3-30 mg/kg; oral administration; PDAPP mice) treatment significantly reduces the hippocampal and cortical levels of Aβ1-x. LY2886721 treatment results in significant reduction of brain parenchymal levels of C99 and sAPPβ.

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 Aβ1-40 and Aβ1-42 are essentially identical, 18.5 and 19.7 nM, respectively.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 Aβ1-40 and Aβ1-42 are comparable in PDAPP neuronal cultures at ～10 nM.

LY2886721 (3-30 mg/kg; oral administration; PDAPP mice) treatment significantly reduces the hippocampal and cortical levels of Aβ1-x. LY2886721 treatment results in significant reduction of brain parenchymal levels of C99 and sAPPβ. Animal Model:Female hemizygous APPV717F transgenic mice (PDAPP) (2-3 months old)Dosage:3 mg/kg, 10 mg/kg, 30 mg/kg Administration:Oral administration Result:Hippocampal and cortical levels of Aβ1-x were significantly reduced.

LY 2886721 | LY-2886721

Metabolic Enzyme/Protease

BACE

BACE

Neurological Disease

Alzheimer Disease

1262036-50-9

390.407

C18H16F2N4O2S

>98% (HPLC)

DMSO: ≥ 42 mg/mL

[H][C@@]12COC[C@@]1(N=C(N)SC2)C1=CC(NC(=O)C2=NC=C(F)C=C2)=CC=C1F |r,c:24,26,28,t:7,13,19,21|

2-Pyridinecarboxamide, N-[3-[(4aS,7aS)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]-4-fluorophenyl]-5-fluoro-

(-20℃)

With Ice Pack

≥ 2 years