P005091 (Synonyms: P005091,P5091) |
Catalog No.GC12067
One-Click Copy Product Info
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P005091 is a potent and selective ubiquitin-specific proteinase 7 (USP7) inhibitor with an EC50 value of 4.2 μM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 882257-11-6
Sample solution is provided at 25 µL, 10mM.
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.
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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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| Cas No. | 882257-11-6 | SDF | |
| Synonyms | P005091,P5091 | ||
| Chemical Name | 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-] | ||
| Formula | C12H7Cl2NO3S2 | M.Wt | 348.22 |
| Solubility | ≥ 17.4 mg/mL in DMSO | Storage | Store at 4°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 | 2.8717 mL | 14.3587 mL | 28.7175 mL |
| 5 mM | 574.3 μL | 2.8717 mL | 5.7435 mL |
| 10 mM | 287.2 μL | 1.4359 mL | 2.8717 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)