A cell-permeable pyrrolylpyrrolidinyl-ethanone compound that directly targets proteasome-associated DUB (deubiquitinating enzyme) USP14 and acts as a potent, active-site-directed and reversible inhibitor of hUSP14 deubiquitinating catalytic activity (IC50=4.7uM for Ub-AMC hydrolysis) with excellent selectivity over proteasome-free USP14 and 8-other hDUBs including IsoT (IC50=100uM), UCH37, BAP1, UCH-L1, UCH-L3, USP15, USP2 and USP7 (IC50>700uM). Shown to enhance proteolysis in cells and induce degradation of misfolded toxic proteins like tau, TDP-43 and GFAP (glial fibrillary acidic protein) in coexpressed-wtMEFs at 50uM and offer protection against oxidative stress-induced cytotoxicity.
Formula:C18H21FN2O
Molecular Weight:300.4
Solubility:DMSO (50mg/ml)
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile buffer or dH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
