Molecular Weight(MW): 672.85
L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.
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The levels of Aβ produced by neuronal differentiated NSCs in response to vehicle (0.1% DMSO), 10μM BSI IV, 10μM L685,458, or the indicated compounds at 3μM or 10μM for 24hours
Sci Rep, 2017 , 7(1):4983. L-685,458 purchased from Selleck.
The level of Aβ produced by SK-N-SH cells in response to vehicle (control) or levodopa at 30 nM either with or without L685,458 pre-treatment. Data are mean + s.e.m., n = 3–4. #p < 0.05 versus the control within the group; ***p < 0.001 versus the corresponding treatment without L685,458.
PLoS One, 2017, 12(3):e0173240. L-685,458 purchased from Selleck.
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Choose Selective Gamma-secretase Inhibitors
|Description||L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.|
L-685,458 inhibits Aβ(40) formation in both Neuro2A and CHO cell lines overexpressing human AβPP695, and in SHSY5Y cells overexpressing the construct spβA4CTF with IC50 of 402 nM, 113 nM, and 48 nM, respectively, with the potency for reduction of Aβ(42) being about 2-fold lower.  In Tca8113 cells, L-685,458 inhibits cell growth by inducing G0–G1 cell cycle arrest and apoptosis.  In a T-cell acute lymphoblastic leukemia cell line, pre-treatment with L-685,458 enhances the anti-proliferative effect of imatinib.  L685,458 also significantly reduces HSV-1 replication in tissue culture by inhibiting signal peptide peptidase (SPP). 
HTRF Immunoassay for Aβ Quantitation:Homogeneous time-resolved fluorescence (HTRF) immunoassay methodology uses fluorescence resonance energy transfer (FRET) between two fluorophores, a donor EuK and a modified allophycocyanine pigment acceptor molecule, XL-665. When in proximity, nonradiative FRET takes place from nitrogen laser-excited EuK to XL-665, resulting in the emission of an amplified long-lived fluorescence signal. Briefly, in a typical 96-well plate assay, each well contains 0.75 nM antibody-EuK, 1.0 nM antibody-biotin, 2.0 nM SA-XL665, and 0.1−0.2 M potassium fluoride. Samples of conditioned cell culture medium or synthetic peptide standards and culture medium alone are added to give a total assay volume of 200 μL/well. Blank values are determined by the inclusion of 1.0 nM nonbiotinylated antibody in place of the biotinylated antibody. Following mixing, the reaction mixture is left at 4 °C to reach equilibrium binding, and then read on the Discovery HTRF microplate analyzer using the manufacturer's recommended settings.
|In vitro||DMSO||100 mg/mL (148.62 mM)|
|Ethanol||6 mg/mL warmed (8.91 mM)|
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