Home Ubiquitin DUB inhibitor - Autophagy activator PR-619 For research use only.

PR-619

PR-619 is a non-selective, reversible inhibitor of the deubiquitinylating enzymes (DUBs) with EC50 of 1-20 μM in a cell-free assay. PR-619 activates autophagy.

PR-619 Chemical Structure

PR-619 Chemical Structure

CAS No. 2645-32-1

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PR-619 Related Products

Signaling Pathway

DUB Signaling Pathways

DUB Signaling Pathway

Biological Activity

Description PR-619 is a non-selective, reversible inhibitor of the deubiquitinylating enzymes (DUBs) with EC50 of 1-20 μM in a cell-free assay. PR-619 activates autophagy.
Targets
JOSD2 [1]
(Cell-free assay)		 SENP6 core [1]
(Cell-free assay)		 UCH-L3 [1]
(Cell-free assay)		 USP4 [1]
(Cell-free assay)		 USP8 [1]
(Cell-free assay)		 Click to View More Targets
1.17 μM(EC50) 2.37 μM(EC50) 2.95 μM(EC50) 3.93 μM(EC50) 4.90 μM(EC50)
In vitro
In vitro

PR-619 is a cell-permeable pyridinamine class broad-spectrum DUB inhibitor whose known targets include ATXN3, BAP1, JOSD2, OTUD5, UCH-L1, UCH-L3, UCH-L5/UCH37, USP1, 2, 4, 5, 7, 8, 9X, 10, 14, 15, 16, 19, 20, 22, 24, 28, 47, 48, VCIP135, YOD1, as well as deISGylase PLpro, deNEDDylase DEN1, and deSUMOlyase SENP6. PR-619 are shown to increase overall protein polyubiquitination in HEK293T cells in a dose- and time-dependent manner (20 to 150 μM, 0.5 to 20 h). PR619 treatment results in upregulation of both K 48 - and K63-linked polyUb chains. PR-619 induces HCT116 cell death with EC50 values of 6.3 μM.[1]
Kinase Assay Ub-PLA2 assay
Recombinant enzymes in 20 mM Tris-HCl, pH 8.0, 2 mM CaCl2 and 2 mM β-mercaptoethanol (DUB assay buffer) are preincubated with single doses or dose ranges of PR-619 or P22077 for 30 minutes in a 96 well plate before the addition of Ub-PLA2 and NBD C6-HPC. The liberation of a fluorescent product within the linear range of the assay is monitored at room temperature using a fluorescence plate reader. Vehicle (2%(v/v) DMSO) and 10 mM N-ethylmaleimide are included as controls. Where ≥60% inhibition is observed, EC50 values are determined using a sigmoidal dose response equation.
Cell Research Cell lines HCT116, HEK293T
Concentrations 0.5-50 μM
Incubation Time 72 h
Method

72 h hours later, 0.2 mg/mL resazurin prepared in phosphate-buffered saline is added to each well and the cells are incubated for an additional 3-6 h. The fluorescence of the resazurin reduction product is measured using Ex=535 nm and Em=590 nm filters on a fluorimeter. The EC50 values are calculated in Prism.
Experimental Result Images Methods Biomarkers Images PMID
Western blot FOXM1 30865895
In Vivo
In vivo

PR-619 enhances the antitumor effect on UC xenograft of nude mice.

Chemical Information & Solubility

Molecular Weight 223.28 Formula

C7H5N5S2
CAS No. 2645-32-1 SDF Download PR-619 SDF
Smiles C1=C(C(=NC(=C1SC#N)N)N)SC#N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 3 mg/mL ( (13.43 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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