Home Ubiquitin DUB inhibitor - Autophagy activator PR-619

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PR-619 DUB inhibitor

Cat.No.S7130

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

Chemical Structure

Molecular Weight: 223.28

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Quality Control

Chemical Information, Storage & Stability

Molecular Weight 223.28 Formula

C7H5N5S2

 Storage (From the date of receipt)
CAS No. 2645-32-1 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1=C(C(=NC(=C1SC#N)N)N)SC#N

Solubility

In vitro
Batch:

DMSO : 3 mg/mL (13.43 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Mechanism of Action

Targets/IC50/Ki
JOSD2 [1]
(Cell-free assay)
1.17 μM(EC50)
SENP6 core [1]
(Cell-free assay)
2.37 μM(EC50)
UCH-L3 [1]
(Cell-free assay)
2.95 μM(EC50)
USP4 [1]
(Cell-free assay)
3.93 μM(EC50)
USP8 [1]
(Cell-free assay)
4.90 μM(EC50)
DEN1 [1]
(Cell-free assay)
4.98 μM(EC50)
USP20 [1]
(Cell-free assay)
5.10 μM(EC50)
USP28 [1]
(Cell-free assay)
6.24 μM(EC50)
USP7 [1]
(Cell-free assay)
6.86 μM(EC50)
USP2 core [1]
(Cell-free assay)
7.20 μM(EC50)
USP15 [1]
(Cell-free assay)
8.23 μM(EC50)
USP5 [1]
(Cell-free assay)
8.61 μM(EC50)
USP47 [1]
(Cell-free assay)
8.87 μM(EC50)
UCH-L5 [1]
(Cell-free assay)
9.26 μM(EC50)
UCH-L1 [1]
(Cell-free assay)
12.8 μM(EC50)
Plpro [1]
(Cell-free assay)
14.2 μM(EC50)
PLA2 [1]
(Cell-free assay)
>50 μM(EC50)
Calpain 1 [1]
(Cell-free assay)
>50 μM(EC50)
CT-L [1]
(Cell-free assay)
>50 μM(EC50)
Cathepsin D [1]
(Cell-free assay)
>50 μM(EC50)
MMP13 [1]
(Cell-free assay)
>50 μM(EC50)
Trypsin [1]
(Cell-free assay)
>50 μM(EC50)
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. This compound is 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). Treatment with this chemical results in upregulation of both K 48 - and K63-linked polyUb chains. It 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.
In vivo

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

Applications

Methods Biomarkers Images PMID
Western blot FOXM1 S7130-WB1 30865895

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