General description

A cell-permeable pyrrolylpyrrolidinyl-ethanone that inhibits the proteasome association-dependent USP14 deubiquitinase (DUB) activity in a reversible manner (IC₅₀ = 4.7 µM against Ub-AMC hydrolysis), exhibiting little or no activity toward 8 other DUBs. Shown to downregulate tau, TDP-43, ATXN3, GFAP, and free Ub levels in MEF cultures in a dose- (25 to 100 µM), time-, and USP14-dependent manner. USP14-catalyzed trimming of protein surface polyubiquitin chains rescues proteasome-bound proteins from proteolytic degradation and thereby prevents the depletion of free ubiquitin pool in cells. Comparing to b-AP15 (Cat. No. 662140), IU1 does not inhibit UCH37/UCH-L5 (IC₅₀ = 700 µM).

A cell-permeable pyrrolylpyrrolidinyl-ethanone that inhibits the proteasome association-dependent USP14 deubiquitinase (DUB) activity in a reversible manner (IC₅₀ = 4.7 M against Ub-AMC hydrolysis), likely by targeting USP14 active site thiol, while exhibiting little or no activity toward 8 other DUBs (﹤10% inhibition of IsoT, UCH37/UCH-L5, BAP1, UCH-L1, UCH-L3, USP2, USP7, and USP15 at 17 M). Shown to downregulate tau, TDP-43, ATXN3, GFAP, and free Ub levels in MEF cultures in a dose- (25 to 100 M), time-, and USP14-dependent manner. Effectively protects HEK293 cells from menadione toxicity (90% vs. 40% viability after 4 h 100 M menadione treatment, respectively, with or without 50 M IU1 pretreatment) by reducing the built-up of oxidized proteins. USP14-catalyzed trimming of protein surface polyubiquitin chains rescues proteasome-bound proteins from proteolytic degradation and thereby prevents the depletion of free ubiquitin pool in cells. Comparing to b-AP15 (Cat. No. 662140), IU1 does not inhibit UCH37/UCH-L5 (IC₅₀ = 700 M).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Lee, B.H., et al. 2010. Nature467, 179.

Packaging

Packaged under inert gas

10 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Warning

Toxicity: Regulatory Review (Z)