PR-619 |
| رقم الكتالوجGC13208 |
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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Cas No.: 2645-32-1
Sample solution is provided at 25 µL, 10mM.
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].
References:
[1] Altun M, et al. (2011) Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem Biol 18:1401-1412
[2] 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.
[3] 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.
| Cell experiment [1]: | |
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Cell lines |
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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. |
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Reaction Conditions |
3-15 µM；24 h, 48 h, and 72 h |
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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]: | |
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Animal models |
8-week-old male nude mice |
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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. |
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Dosage form |
10 mg/kg; i.p. |
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Applications |
PR-619 showed significant anti-tumor effects on xenograft tumors from both cell lines. |
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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. |
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| 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 |
| الذوبان | ≥ 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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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Quality Control & SDS
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- Purity: >98.00%
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