PR-619
(Synonyms: 2,6-二氨基-3,5-二硫氰基吡啶) 目录号 : GC13208
PR-619是一种广谱的去泛素酶抑制剂。
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.
PR-619是一种广谱的去泛素酶抑制剂。PR-619在HEK 293T细胞中表现出强大的DUB抑制活性(5-20µM)和生长抑制活性,IC50为2µM[1]。
40µM的PR-619在K562细胞中诱导高于背景的TOP2A和TOP2B信号[2]。体外疗效测试显示,PR-619对JJ012和SW1353人软骨肉瘤细胞系的抗肿瘤作用,PR-6119浓度范围为2.5至17.5 µM,持续24和48小时。PR-619以剂量和时间依赖的方式显著降低软骨肉瘤细胞的生存能力[3]。在体外,PR-619处理(0-80µM)在24和48小时以剂量依赖的方式显著抑制细胞活力。此外,PR-619(20µM)处理48小时可显著诱导顺铂耐药T24/R细胞凋亡[4]。在体内,用PR-619(每天10 mg/kg)腹膜内处理小鼠,增强了T24/R异种移植小鼠模型中顺铂的抗肿瘤作用[4]。
| 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. | |
| Cas No. | 2645-32-1 | SDF | |
| 别名 | 2,6-二氨基-3,5-二硫氰基吡啶 | ||
| 化学名 | (2,6-diamino-5-thiocyanatopyridin-3-yl) thiocyanate | ||
| Canonical SMILES | C1=C(C(=NC(=C1SC#N)N)N)SC#N | ||
| 分子式 | C7H5N5S2 | 分子量 | 223.28 |
| 溶解度 | ≥ 11.15mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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