PR-619

Catalog No.S7130 Batch:S713004

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Technical Data

Formula

C7H5N5S2
Molecular Weight 223.28 CAS No. 2645-32-1
Solubility (25°C)* In vitro DMSO 4 mg/mL (17.91 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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)		 View More
1.17 μM(EC50) 2.37 μM(EC50) 2.95 μM(EC50) 3.93 μM(EC50) 4.90 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. 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]
In vivo

PR-619 enhances the antitumor effect of cisplatin on a cisplatin-naive and cisplatin-resistant UC xenograft of nude mice.

Protocol (from reference)

Kinase Assay:

[1]
  • 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 Assay:

[1]
  • 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.

Customer Product Validation

Data from [Data independently produced by , , Front Pharmacol, 2017, https://doi.org/10.3389/fphar.2017.00565]

Data from [Data independently produced by , , Front Pharmacol, 2018, 8:565]

Data from [Data independently produced by , , Anim Reprod Sci, 2017, 187:64-73]

Selleck's PR-619 has been cited by 54 publications

Noncanonical function of folate through folate receptor 1 during neural tube formation [ Nat Commun, 2024, 15(1):1642] PubMed: 38388461
Precise pancreatic cancer therapy through targeted degradation of mutant p53 protein by cerium oxide nanoparticles [ J Nanobiotechnology, 2023, 21(1):117] PubMed: 37005668
Comparative proteomic and phosphoproteomic analysis reveals differential heat response mechanism in two congeneric oyster species [ Ecotoxicol Environ Saf, 2023, 263:115197] PubMed: 37451098
Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models [ Biomedicines, 2023, 10.3390/biomedicines11030759] PubMed: 36979739
A Novel Recognition by the E3 Ubiquitin Ligase of HSV-1 ICP0 Enhances the Degradation of PML Isoform I to Prevent ND10 Reformation in Late Infection [ Viruses, 2023, 15(5)1070] PubMed: 37243155
Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models [ Biomedicines, 2023, 11(3)759] PubMed: 36979739
An indispensable role of TAZ in anoikis resistance promoted by OTUB1 deubiquitinating enzyme in basal-like triple-negative breast cancer cells [ Biochem Biophys Res Commun, 2023, 649:1-9] PubMed: 36738577
Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis [ Cell Res, 2022, 1-17] PubMed: 35821088
Substitution of PINK1 Gly411 modulates substrate receptivity and turnover [ Autophagy, 2022, 1-22.] PubMed: 36469690
Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation [ Cell Death Differ, 2022, 10.1038/s41418-022-00983-4] PubMed: 35379950

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.