L-685458

L-685458 is a potent transition state analog (TSA) γ-secretase inhibitor (GSI). L-685458 inhibits amyloid β-protein precursor γ-secretase activity with IC50 of 17 nM, shows greater than 50-100-fold selectivity over other aspartyl proteases tested. L685458 inhibits γ-secretase-mediated cleavage of APP-C99 and Notch-100 with IC50s of 301.3 nM and 351.3 nM, respectively. L-685458 can be used for the research of alzheimer’s disease (AD) and cancers.

References

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