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PR-619

Catalog No.GC13208

PR-619 is a broad-spectrum DUB (deubiquitinating enzyme) inhibitor. PR-619 has demonstrated robust DUB inhibitory activity (5-20 µM) and growth inhibitory activity with IC50 of 2 µM in HEK 293T cells..

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PR-619 Chemical Structure

Cas No.: 2645-32-1

Size Price Stock Qty
5mg
$29.00
In stock
10mM (in 1mL DMSO)
$58.00
In stock
25mg
$75.00
In stock
100mg
$204.00
In stock

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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 1 publications

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

Preparation Method

T24 and BFTC-905 cells were treated with various concentrations of PR-619 (3-15 µM) for 24 h, 48 h, and 72 h, respectively. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Reaction Conditions

3-15 µM;24 h, 48 h, and 72 h

Applications

PR-619 effectively induced cytotoxicity and apoptosis in both T24 and BFTC cells in a dose- and time-dependent manner. Additionally, we found that PR-619 induced cytotoxicity in low-grade RT-4 UC cells and cisplatin-resistant UC cells (T24/R) in a dose- and time-dependent manner.

Animal experiment [2]:

Animal models

8-week-old male nude mice

Preparation Method

A total of 5 × 105 JJ012 or SW1353 cells were suspended in 200 µL of serum-free medium and an equal amount of Matrigel. The cell suspension thus derived was then injected subcutaneously into the dorsal side of 8-week-old male nude mice. When the tumor grew to ~150 mm3, mice were randomly assigned to either the PR-619 treatment group or the control group. Mice in the treatment group received PR-619 10 mg/kg intraperitoneal injection twice daily for 48 days. Mice in the untreated control group received an injection of DMSO solution.

Dosage form

10 mg/kg; i.p.

Applications

PR-619 showed significant anti-tumor effects on xenograft tumors from both cell lines.

References:

[1] Kuo KL, et al. The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study. Cells. 2019 Oct 17;8(10):1268.
[2] Lin WC, et al. Anti-tumor effects of deubiquitinating enzyme inhibitor PR-619 in human chondrosarcoma through reduced cell proliferation and endoplasmic reticulum stress-related apoptosis. Am J Cancer Res. 2023 Jul 15;13(7):3055-3066.

Background

PR-619 is a broad-spectrum DUB (deubiquitinating enzyme) inhibitor. PR-619 has demonstrated robust DUB inhibitory activity (5-20 µM) and growth inhibitory activity with IC50 of 2 µM in HEK 293T cells[1].

PR-619 at 40 µM induced an above-background TOP2A and TOP2B signal in K562 cells[2]. In vitro efficacy test shown that the anti-tumor effects of PR-619 on the JJ012 and SW1353 human chondrosarcoma cell lines, with PR-619 concentrations ranging from 2.5 to 17.5 µM for 24 and 48 h. PR-619 significantly reduced the viability of chondrosarcoma cells in a dose- and time-dependent manner[3]. In vitro, PR-619 treatment (0 - 80 µM) significantly inhibited cell viability at 24 and 48 h in a dose-dependent manner. Furthermore, PR-619 (20 µM) treatment for 48 h significantly induced apoptosis in cisplatin-resistant T24/R cells[4].

In vivo, mice were intraperitoneally treated with PR-619 (10 mg/kg each day) enhanced the antitumor effect of cisplatin in a xenograft mouse model of T24/R[4].

Altun M, et al. (2011) Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem Biol 18:1401-1412.

Cowell IG, et al. The Deubiquitinating Enzyme Inhibitor PR-619 is a Potent DNA Topoisomerase II Poison. Mol Pharmacol. 2019 Nov;96(5):562-572.

Lin WC, et al. Anti-tumor effects of deubiquitinating enzyme inhibitor PR-619 in human chondrosarcoma through reduced cell proliferation and endoplasmic reticulum stress-related apoptosis. Am J Cancer Res. 2023 Jul 15;13(7):3055-3066.

[4] Hsu FS, et al. PR-619, a General Inhibitor of Deubiquitylating Enzymes, Diminishes Cisplatin Resistance in Urothelial Carcinoma Cells through the Suppression of c-Myc: An In Vitro and In Vivo Study. Int J Mol Sci. 2021 Oct 28;22(21):11706.

References:

Chemical Properties

Cas No. 2645-32-1 SDF
Chemical Name (2,6-diamino-5-thiocyanatopyridin-3-yl) thiocyanate
Canonical SMILES C1=C(C(=NC(=C1SC#N)N)N)SC#N
Formula C7H5N5S2 M.Wt 223.28
Solubility ≥ 11.15mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 4.4787 mL 22.3934 mL 44.7868 mL
5 mM 0.8957 mL 4.4787 mL 8.9574 mL
10 mM 0.4479 mL 2.2393 mL 4.4787 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

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