Description
PR-619 (2645-32-1) is a nonselective, reversible inhibitor of cysteine-reactive deubiquitinating enzymes (DUBs; 5-20 μM)1. PR-619 is highly useful for preserving ubiquitinated proteins during cell lysis. DUBs become unregulated in cell lysates and will act quickly to deubiquitinate proteins of interest during cell lysis. To preserve maximum amounts of ubiquitinated protein, include PR-619 (50-100 μM) in lysis buffers. PR-619 is also useful for interrogating the role of DUBs in intact cell systems2, and treatment of cells results in an overall accumulation of ubiquitinated proteins and many other phenotypes.
Enzyme inhibitor
This non-selective, cell-permeable pyridinamine (FW = 223.28 g/mol; CAS
2645-32-1) reversibly inhibits deubiquitinylating enzymes, or DUBs, with
EC50 values typically in the 1 to 20 μM range. Targets: ATXN3, BRCA1
Associated Protein-1 (or BAP1), Josephin domain containing-2 (or
JOSD2), Ovarian Tumor Domain-containing-5 (or OTUD5), Ubiquitin
Carboxyl-Terminal Hydrolase Isozyme-1 (or UCH-L1, UCH-L3, UCH-L5,
UCH37, Ubiquitin-Specific Peptidase-1 (or USP-1), USP-2, USP-4, USP-5,
USP-7, USP-8, USP-9X, USP-10, USP-14, USP15, USP-16, USP-19, USP-
20, USP-22, USP-24, USP-28, USP-47, USP-48, Valosin-containing protein
(or VCIP135), YOD1, as well as deISGylase PLpro, deNEDDylase DEN1,
and deSUMOlyase SENP6.
References
1) Altun?et al. (2011),?Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes; Chem. Biol.,?18?1401
2) Seiberlich?et al. (2012),?The small molecule inhibitor PR-619 of deubiquitinating enzymes affects the microtubule network and causes protein aggregate formation in neural cells: implications for neurodegenerative diseases; Biochim. Biophys. Acta,?1823?2057
