L-685,458 is an inhibitor of γ-secretase (IC50 = 17 nM).1 It is selective for γ-secretase over HIV-1, cathepsin D, trypsin, HepC3 NS3, papain, and calpain I proteases (IC50s = >10 nM). L-685,458 inhibits production of amyloid-β (1-40) (Aβ40; Item No. 21617) and Aβ42 (Item No. 20574) in Neuro2A cells transfected with human amyloid precursor protein (APP; IC50s = 402 and 775 nM, respectively). It is also an inhibitor of Notch signaling that blocks hypoxia-induced activity of the Notch-responsive reporters 12xCSL and CBF1 in isolated rat intervertebral disc cells.2WARNING This product is not for human or veterinary use.