L-685,458

Catalog No.S7673

L-685,458 Chemical Structure

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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2 Customer Reviews

  • 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.

Purity & Quality Control

Choose Selective Gamma-secretase Inhibitors

Biological Activity

Description L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.
Targets
Gamma-secretase [1]
17 nM(Ki)
In vitro

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. [1] In Tca8113 cells, L-685,458 inhibits cell growth by inducing G0–G1 cell cycle arrest and apoptosis. [2] In a T-cell acute lymphoblastic leukemia cell line, pre-treatment with L-685,458 enhances the anti-proliferative effect of imatinib. [3] L685,458 also significantly reduces HSV-1 replication in tissue culture by inhibiting signal peptide peptidase (SPP). [4]

Protocol

Kinase Assay:[1]
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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.
Cell Research:[2]
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  • Cell lines: Tca8113 cells
  • Concentrations: ~5.0 μM
  • Incubation Time: 48 h
  • Method: The in vitro growth rate of Tca8113 cells treated with L-685,458, is measured by MTT. Briefly, Tca8113 cells are seeded in 96-well plates. On the day of harvest, 100 μL of spent medium is replaced with an equal volume of fresh medium containing 10% MTT 5 mg ml−1 stock. Plates are incubated at 37°C for 4 h, then 100 μl of DMSO is added to each well, and then plates are shaken at room temperature for 10 min. The absorbance is measured at 570 nm.
    (Only for Reference)

References

Solubility (25°C)

In vitro DMSO 100 mg/mL (148.62 mM)
Ethanol 6 mg/mL warmed (8.91 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 672.85
Formula

C39H52N4O6

CAS No. 292632-98-5
Storage powder
Synonyms N/A

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Gamma-secretase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID