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[1][2].

Product Specifications

CAS Number

[292632-98-5]

Product Name Alternative

L-685,458

UNSPSC

12352005

Hazard Statement

H302, H315, H319, H335

Target

Apoptosis; γ-secretase

Type

Reference compound

Related Pathways

Apoptosis; Neuronal Signaling; Stem Cell/Wnt

Applications

Cancer-programmed cell death

Field of Research

Neurological Disease; Cancer

Assay Protocol

https://www.medchemexpress.com/L-685458.html

Purity

99.48

Solubility

DMSO : 83.3 mg/mL (ultrasonic; warming)

Smiles

O=C(N)[C@H](CC1=CC=CC=C1)NC([C@H](CC(C)C)NC([C@H](CC2=CC=CC=C2)C[C@@H](O)[C@@H](NC(OC(C)(C)C)=O)CC3=CC=CC=C3)=O)=O

Molecular Formula

C39H52N4O6

Molecular Weight

672.85

Precautions

H302, H315, H319, H335

References & Citations

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