L-685,458

Names

[ Name ]:
L-685,458

[Synonym ]:
(5S)-(t-Butoxycarbonylamino)-6-phenyl-(4R)hydroxy-(2R)benzylhexanoyl)-L-leu-L-phe-amide
L-685458

Biological Activity

[Description]:

L-685458 is a potent inhibitor of Amyloid β-Protein precursor γ-secretase activity with IC50 of 17 nM, shows greater than 50-100-fold selectivity over other aspartyl proteases tested.IC50 value: 17 nMTarget: γ-secretasein vitro: L-685458 is a Notch inhibitor. L-685458 blocks Notch activation in the two cell lines in terms of reduced cytoplasmic distribution and almost diminished nuclear labelling of Hes1 proteins. [2] L-685458 is a γ-secretase inhibitor. [3]

[Related Catalog]:

Signaling Pathways >> Neuronal Signaling >> γ-secretase

Signaling Pathways >> Stem Cell/Wnt >> γ-secretase

Research Areas >> Neurological Disease

[References]

[1]. Shearman MS, et al. L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity. Biochemistry. 2000 Aug 1;39(30):8698-8704.

[2]. Zhang P, et al. Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells. Genes Cancer. 2014 May;5(5-6):154-164.

[3]. Jeon JH, et al. Glucosamine-induced OGT activation mediates glucose production through cleaved Notch1 and FoxO1, which coordinately contributed to the regulation of maintenance of self-renewal in mouse embryonic stem cells. Stem Cells Dev. 2014 Sep 1;23(1

[Related Small Molecules]

DAPT (GSI-IX) | RO4929097 | YO-01027 | PF-3084014 | LY-411575 | MK-0752 | Avagacestat | Semagacestat(LY450139) | Z-Ile-Leu-aldehyde | E 2012 | gamma-secretase modulator 1 | NGP555 | BMS 299897 | gamma-secretase modulator 3 | CHF5074

Chemical & Physical Properties

[ Molecular Formula ]:
C₃₉H₅₂N₄O₆

[ Molecular Weight ]:
672.85300

[ Exact Mass ]:
672.38900

[ PSA ]:
159.85000

[ LogP ]:
6.34900

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ Safety Phrases ]:
22-24/25

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

Articles

RAGE inhibition in microglia prevents ischemia-dependent synaptic dysfunction in an amyloid-enriched environment.

J. Neurosci. 34(26) , 8749-60, (2014)

Ischemia is known to increase the deleterious effect of β-amyloid (Aβ), contributing to early cognitive impairment in Alzheimer's disease. Here, we investigated whether transient ischemia may function...

Suppression of Notch signaling in the neonatal mouse ovary decreases primordial follicle formation.

Endocrinology 150 , 1014-24, (2009)

Notch signaling directs cell fate during embryogenesis by influencing cell proliferation, differentiation, and apoptosis. Notch genes are expressed in the adult mouse ovary, and roles for Notch in reg...

L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity.

Biochemistry 39 , 8698, (2000)

Progressive cerebral amyloid beta-protein (A beta) deposition is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). Elevated levels of A beta(42) peptide formation have b...