|JLK 6 Catalog No.GC13619|
Sample solution is provided at 25 µL, 10mM.
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|Solubility||<22.56mg/ml in DMSO; <5.64mg/ml in ethanol||Storage||Store at RT|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|
|Shipping Condition||Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
JLK 6, an isocoumarin, is a selective inhibitor of γ-secretase, with an IC50 value between 10 μM-1 mM [1, 2].
The enzyme γ-secretase catalyzes the cleavage of β-Amyloid precursor protein (βAPP) to produce Amyloid β-peptide (Aβ). Aβ is a part of the plaque present in the brain of patients with Alzheimer’s disease. γ-secretase also targets other substrates like Notch. Notch is a transmembrane protein which is involved in important functions during different stages in development, both embryonic and adulthood .
HEK293 cells were used. In these cells, wild-type βAPP was overexpressed (962 fmol/mL in 35-mm wells). JLK6 markedly reduced Aβ secreted from these cells. Interestingly, JLK6 potentiated the recovery of two fragments. Immunological characterization indicated that one fragment was labelled with a specific antibody against the Asp1 residue of Aβ. JLK6 also inhibited the Aβ recovery from cells overexpressing Swedish-mutant βAPP to a similar extent .
In the zebrafish embryo, JLK isocoumarin inhibitors did not change the Notch pathway responsible for somitogenesis. Unlike other γ-secretase inhibitors, these agents did not affect E-cadherin processing. JLKs did not inhibit α-secretase, β-site APP cleaving enzymes (BACE) 1 and BACE2, GSK3β kinase and proteasome. JLK inhibitors prevented Aβ production without inducing unwanted cleavages of other proteins .
. Petit A, Pasini A, Alves Da Costa C, et al. JLK isocoumarin inhibitors: Selective γ-secretase inhibitors that do not interfere with notch pathway in vitro or in vivo. Journal of neuroscience research, 2003, 74(3): 370-377.
. Petit A, Bihel F, da Costa CA, et al. New protease inhibitors prevent γ-secretase-mediated production of Aβ40/42 without affecting Notch cleavage. Nature cell biology, 2001, 3(5): 507-511.