L-685,458

Name: L-685,458
Brand: Tocris Bioscience
SKU: 2627

Tocris Bioscience, part of Bio-Techne | Catalog # 2627

Citations (39)

COA / SDS

Potent and selective γ-secretase inhibitor

Key Product Details

Description:	Potent and selective γ-secretase inhibitor
Alternative Names:	L 458,γ-Secretase Inhibitor X
Chemical Name:	(5S)-(tert-Butoxycarbonylamino)-6-phenyl-(4R)-hydroxy-(2R)-benzylhexanoyl)-L-leucy-L-phenylalaninamide
Purity:	≥97% (HPLC)
Molecular Weight:	672.85

View Full Technical Details for L-685,458

Technical Data
Citations

Biological Activity for L-685,458

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.

Technical Data for L-685,458

M. Wt	672.85
Formula	C₃₉H₅₂N₄O₆
Storage	Store at -20°C
Purity	≥97% (HPLC)
CAS Number	292632-98-5
PubChem ID	5479543
InChi Key	MURCDOXDAHPNRQ-ZJKZPDEISA-N
Smiles	O[C@H](C[C@@H](CC1=CC=CC=C1)C(N[C@@H](CC(C)C)C(N[C@@H](CC3=CC=CC=C3)C(N)=O)=O)=O)[C@H](CC2=CC=CC=C2)NC(OC(C)(C)C)=O

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.

Tocris products are intended for laboratory research use only, unless stated otherwise.

Solubility for L-685,458

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
Solubility	DMSO	10.09	15

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 will affect the solvent volumes required to prepare stock solutions.

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

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References for L-685,458

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