P005091
(Synonyms: P005091,P5091) 目录号 : GC12067
P005091是一种有效的选择性泛素特异性蛋白酶7 (USP7) 抑制剂，EC50 值为4.2 μM。
Cas No.:882257-11-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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Cell experiment [1]: |
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Cell lines |
Human MM cell lines |
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Preparation method |
MM.1S cells were pretreated with inhibitors of caspase-8, caspase-9, or pan-caspase for 1h, and then P005091 (12.5μM) or bortezomib (10nM) was added for another 24 h, followed by analysis of viability. |
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Reaction Conditions |
12.5μM; 24 h |
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Applications |
P005091 induces a decrease in viability of various MM cell lines. |
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Animal experiment [2]: |
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Animal models |
BALB/c mice |
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Preparation method |
Mice received subcutaneous injections of CT26 cells (5×105 cells in 100 µL PBS). Tumor growth was evaluated by measuring the length and width of the tumor mass with calipers every 2 days. P005091 (5, 10 mg/kg, intraperitoneal every day) was administrated from day 3 onward. Intraperitoneal injected anti-PD-1 (5mg/kg, every 3 days) was used as a positive control. Cytokines, including IL-10, TNF-α, and IFN-γ, were measured in serum. |
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Dosage form |
5, 10 mg/kg; i.p. |
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Applications |
P005091 treatment decreased the tumor weight. P005091 treatment decreased IL-10 mRNA level in tumor tissue while elevated mRNA level of IFN-γ and TNF-α. |
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References: [1] Chauhan D, et al. A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance[J]. Cancer Cell. 2012 Sep 11;22(3):345-58. [2]Fu C , Zhu X , Xu P ,et al.Pharmacological inhibition of USP7 promotes antitumor immunity and contributes to colon cancer therapy[J].OncoTargets and Therapy, 2019, Volume 12:609-617. |
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P005091 is a potent and selective ubiquitin-specific proteinase 7 (USP7) inhibitor with an EC50 value of 4.2 μM[1]. P005091 is a trisubstituted thiophene with dichlorophenylthio, nitro, and acetyl substituents that mediates anti-USP7 activity and may be a potential therapeutic agent for the treatment of HO-1-overexpressing liver cancer [2]. P005091 can inhibit the development of hepatoblastoma and the PI3K/AKT pathway [3].
In vitro, treatment of multiple myeloma cell lines with P005091 (12.5μM) for 24 hours resulted in a decrease in cell viability and inhibited USP7 deubiquitination activity in MM cells without blocking proteasome activity [1]. P005091 (3μM) treated MM.1S cells for 12 hours induced cytotoxicity, accompanied by the upregulation of p53 and p21[4]. P005091 (10 μM) treated CUTLL1 and JURKAT cells for 24 hours, which significantly increased the polyubiquitination of SF3B1 protein and reduced the level of SF3B1 protein [5].
In vivo, intraperitoneal injection of P005091 (10mg/kg) in tumor-bearing mice significantly inhibited tumor cell growth and reduced PCNA protein expression in tumor cells [6]. P005091 treatment also reduced IL-10 mRNA levels in tumor tissue while increasing IFN-γ and TNF-α mRNA levels [6]. Tail vein injection of P005091 (10mg/kg) significantly reduced the protein level of MyD88 in mouse cells [7].
References:
[1] Chauhan D, et al. A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance[J]. Cancer Cell. 2012 Sep 11;22(3):345-58.
[2] Gao M , Qi Z , Deng M ,et al.The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1[J].Oncogene, 2022(33):41.
[3] Ye M , He J , Zhang J ,et al. USP7 promotes hepatoblastoma progression through activation PI3K/AKT signaling pathway[J].Cancer biomarkers : section A of Disease markers.2021.
[4] Das D S , Ray A , Das A ,et al.A Novel Hypoxia-Selective Epigenetic Agent RRx-001 Triggers Apoptosis and Overcomes Drug Resistance in Multiple Myeloma Cells[J]. Leukemia Research Fund, U.K, 2016, 30(11).
[5]Han C , Khodadadi-Jamayran A , Lorch A H ,et al. SF3B1 homeostasis is critical for survival and therapeutic response in T cell leukemia[J].Science advances, 2022, 8(3):eabj8357.
[6]Fu C, Zhu X , Xu P ,et al. Pharmacological inhibition of USP7 promotes antitumor immunity and contributes to colon cancer therapy[J].OncoTargets and Therapy, 2019, Volume 12:609-617.
[7]Na Zhang, Fei Wang, et al. USP7 Promotes deubiquitination and stabilization of MyD88 to enhance immune responses[J].Front. Immunol., 12 August 2022.
P005091是一种有效的选择性泛素特异性蛋白酶7 (USP7) 抑制剂，EC50 值为4.2 μM[1]。P005091是一种三取代噻吩，具有二氯苯硫基、硝基和乙酰取代基，介导抗USP7活性，可能是治疗HO-1过表达肝癌的潜在治疗剂[2]。P005091可抑制肝母细胞瘤的发展和PI3K/AKT通路[3]。
在体外，P005091（12.5μM）处理多发性骨髓瘤细胞系24h，会导致细胞活力下降，抑制MM细胞中的USP7去泛素化活性，而不阻断蛋白酶体活性[1]。P005091（3μM）处理MM.1S细胞12小时诱导了细胞毒性，伴随p53和p21的上调[4]。P005091（10 μM）处理CUTLL1和JURKAT细胞24h，使SF3B1蛋白的多泛素化显著增加，降低了SF3B1蛋白的水平[5]。
在体内，P005091（10mg/kg）腹膜内注射治疗荷瘤小鼠，显著抑制肿瘤细胞生长，降低了肿瘤细胞PCNA蛋白表达[6]。P005091治疗还降低了肿瘤组织中IL-10 mRNA水平，同时升高了IFN-γ和TNF-α的mRNA水平[6]。P005091（10mg/kg）尾静脉注射显著降低了小鼠细胞中MyD88的蛋白水平[7]。
| Cas No. | 882257-11-6 | SDF | |
| 别名 | P005091,P5091 | ||
| 化学名 | 1-[5-(2,3-dichlorophenyl)sulfanyl-4-nitrothiophen-2-yl]ethanone | ||
| Canonical SMILES | CC(=O)C1=CC(=C(S1)SC2=C(C(=CC=C2)Cl)Cl)[N+](=O)[O-] | ||
| 分子式 | C12H7Cl2NO3S2 | 分子量 | 348.22 |
| 溶解度 | ≥ 17.4 mg/mL in DMSO | 储存条件 | Store at 4°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 | 2.8717 mL | 14.3587 mL | 28.7175 mL |
| 5 mM | 0.5743 mL | 2.8717 mL | 5.7435 mL |
| 10 mM | 0.2872 mL | 1.4359 mL | 2.8717 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。
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