Home Proteases Secretase inhibitor L-685,458

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L-685,458 Secretase inhibitor

Cat.No.S7673

L-685,458 is a specific and potent inhibitor of A beta PP gamma-secretase activity with Ki of 17 nM.
L-685,458 Secretase inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 672.85

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S767301 DMSO]100 mg/mL]false]Ethanol]6 mg/mL]false]Water]Insoluble]false Purity: 99.99%
99.99

Chemical Information, Storage & Stability

Molecular Weight 672.85 Formula

C39H52N4O6

 Storage (From the date of receipt)
CAS No. 292632-98-5 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC(C)CC(C(=O)NC(CC1=CC=CC=C1)C(=O)N)NC(=O)C(CC2=CC=CC=C2)CC(C(CC3=CC=CC=C3)NC(=O)OC(C)(C)C)O

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (148.62 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 6 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Mechanism of Action

Targets/IC50/Ki
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, this compound 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 this chemical enhances the anti-proliferative effect of imatinib. [3] It also significantly reduces HSV-1 replication in tissue culture by inhibiting signal peptide peptidase (SPP). [4]
Kinase Assay
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
References

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