Chemical Name: (5S)-(tert-Butoxycarbonylamino)-6-phenyl-(4R)-hydroxy-(2R)-benzylhexanoyl)-L-leucy-L-phenylalaninamide
Biological ActivityL-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.
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.
Regulation of CXCR4 by the Notch ligand delta-like 4 in endothelial cells.
Williams CK, Segarra M, Sierra Mde L, Sainson RC, Tosato G, Harris AL
Cancer Res., 2008;68(6):1889-95.
L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid-β-protein precursor γ-secretase activity.
Shearman et al.
Up-regulation of the Notch ligand delta-like 4 inhibits VEGF-induced endothelial cell function.
Williams et al.
Citations for L-685,458
The citations listed below are publications that use Tocris products. Selected citations for L-685,458 include:
8 Citations: Showing 1 - 8
Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis.
Authors: Mentrup Et al.
Spatial patterning of liver progenitor cell differentiation mediated by cellular contractility and Notch signaling.
Authors: Kaylan Et al.
APP upregulation contributes to retinal ganglion cell degeneration via JNK3.
Authors: Liu Et al.
Cell Death Differ 2018;25:661
HIV-1 counteracts an innate restriction by amyloid precursor protein resulting in neurodegeneration.
Authors: Chai Et al.
Nat Commun 2017;8:1522
Differential Inhibition of Signal Peptide Peptidase Family Members by Established γ-Secretase Inhibitors.
Authors: Ran Et al.
PLoS One 2015;10:e0128619
RAGE inhibition in microglia prevents ischemia-dependent synaptic dysfunction in an amyloid-enriched environment.
Authors: Origlia Et al.
J Neurosci 2014;34:8749
γ-Secretase processing and effects of γ-secretase inhibitors and modulators on long Aβ peptides in cells.
Authors: Ran Et al.
J Biol Chem 2014;289:3276
Canonical Notch signalling is inactive in urothelial carcinoma.
Authors: Greife Et al.
BMC Cancer 2014;14:628
No product specific FAQs exist for this product, however you mayView all Small Molecule FAQs
Reviews for L-685,458
There are currently no reviews for this product. Be the first to review L-685,458 and earn rewards!
Have you used L-685,458?
Submit a review and receive an Amazon gift card.
$25/€18/£15/$25CAN/¥75 Yuan/¥1250 Yen for a review with an image
$10/€7/£6/$10 CAD/¥70 Yuan/¥1110 Yen for a review without an image