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^[1][2].

L-685458 reduces both Aβ(40) and Aβ(42) peptide formation in 3 different cells. It against Neuro2A h AβPP695, CHO h AβPP695, and SHSY5 spβA4CTF reduction of Aβ(40) with IC₅₀ values of 402 nM, 113 nM and 48 nM, respectively. And the IC₅₀ values are 775 nM, 248 nM, 67 nM, respectively^[1].
L-685458 (5-40 μM; 24 hours) leads to a dramatic downregulation of Hes-1 in 786-O cells^[3].
L-685458 has inhibitory effects in hepatoma cell lines, it against Huh7, HepG2, HLE and SKHep1 cells with IC₅₀ of 12.91 μM, 12.69 μM, 21.76 μM and 12.18 μM, respectively^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Shearman, M.S., Beher, D., Clarke, E.E., Lewis, H.D., Harrison, T., Hunt, P.,  [Content Brief]

  [2]. Guanghui Yang, et al. Structural basis of γ-secretase inhibition and modulation by small molecule drugs. Cell. 2021 Jan 21;184(2):521-533.e14.  [Content Brief]

  [3]. Jonas Sjölund, et al. Suppression of renal cell carcinoma growth by inhibition of Notch signaling in vitro and in vivo. J Clin Invest. 2008 Jan;118(1):217-28.  [Content Brief]

  [4]. Kazunori Kawaguchi, et al. Jagged1 DNA Copy Number Variation Is Associated with Poor Outcome in Liver Cancer. Am J Pathol. 2016 Aug;186(8):2055-2067.  [Content Brief]