L-685,458

Product Description

L-685,458 is a potent and selective γ-secretase inhibitor (IC₅₀ = 17 nM) that displays > 50-fold selectivity over a range of aspartyl, serine and cysteine proteases. L-685,458 binds with high affinity to the related aspartyl protease, signal peptide peptidase (SPP; K_D = 5.1 nM), and inhibits SPP expressed in HEK293 cells (IC₅₀ = 10 μM). L-685,458 exhibits equal potency for inhibition of Aβ40 and Aβ42 peptides (IC₅₀ values are 48 and 67 nM respectively in human neuroblastoma cells). It also regulates CXCR4 and VEGFR2 expression through inhibition of Notch signaling in vitro.

Solubility

Preparing Stock Solutions for L-685,458

The following data is based on the product molecular weight 672.85

Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which all affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:

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Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
0.15 mM	9.91 mL	49.54 mL	99.08 mL
0.75 mM	1.98 mL	9.91 mL	19.82 mL
1.5 mM	0.99 mL	4.95 mL	9.91 mL
7.5 mM	0.20 mL	0.99 mL	1.98 mL

Calculators

Background References

References are publications that support the biological activity of the product.

• Iben Signal peptide peptidase and gamma-secretase share equivalent inhibitor binding pharmacology. J.Biol.Chem. 2007 PMID: 17932033
• Williams Up-regulation of the Notch ligand delta-like 4 inhibits VEGF-induced endothelial cell function. Blood 2006 PMID: 16219802
• Williams Regulation of CXCR4 by the Notch ligand delta-like 4 in endothelial cells. Cancer Res. 2008 PMID: 18339870
• Shearman L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid-β-protein precursor γ-secretase activity. Biochemistry 2000 PMID: 10913280