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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)
Citations (8)
Literature (2)

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; KD = 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
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 Data for L-685,458

Solvent Max Conc. mg/mL Max Conc. mM
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.

Select a batch to recalculate based on the batch molecular weight:
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 0.2 mL 0.99 mL 1.98 mL

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Product Datasheets for L-685,458

Certificate of Analysis / Product Datasheet
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References for L-685,458

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

Shearman et al (2000) L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid-β-protein precursor γ-secretase activity. Biochemistry 39 8698 PMID: 10913280

Williams et al (2006) Up-regulation of the Notch ligand delta-like 4 inhibits VEGF-induced endothelial cell function. Blood 107 931 PMID: 16219802

Williams et al (2008) Regulation of CXCR4 by the Notch ligand delta-like 4 in endothelial cells. Cancer Res. 68 1889 PMID: 18339870

Iben et al (2007) Signal peptide peptidase and gamma-secretase share equivalent inhibitor binding pharmacology. J.Biol.Chem. 282 36829 PMID: 17932033

If you know of a relevant reference for L-685,458, please let us know.

View Related Products by Product Action

View all γ-Secretase Inhibitors

Keywords: L-685,458, L-685,458 supplier, L458, Potent, selective, γ-secretase, gamma-secretase, inhibitors, inhibits, Aβ4, beta40, β42, beta42, Proteinases, Proteases, b-amyloid, β-Amyloid, beta-Amyloid, Precursor, Protein, APP, beta, L685458, amyloidbeta, amyloidb, amyloidβ, inhibitor, X, SPP, SP, L, 458, gamma-Secretase, Inhibitor, Gamma-Secretase, Amyloid, Beta, Peptides, Other, 2627, Tocris Bioscience

8 Citations for L-685,458

Citations are publications that use Tocris products. Selected citations for L-685,458 include:

Ran et al (2014) γ-Secretase processing and effects of γ-secretase inhibitors and modulators on long Aβ peptides in cells. J Biol Chem 289 3276 PMID: 24352661

Origlia et al (2014) RAGE inhibition in microglia prevents ischemia-dependent synaptic dysfunction in an amyloid-enriched environment. J Neurosci 34 8749 PMID: 24966375

Mentrup et al (2022) Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis. Nat.Commun. 13 1880 PMID: 35388002

Greife et al (2014) Canonical Notch signalling is inactive in urothelial carcinoma. BMC Cancer 14 628 PMID: 25167871

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Literature in this Area

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