P005091
P005091 is a selective, potent inhibitor of USP7 deubiquitylating activity, which is demonstrated to downregulate claspin and phosphorylation of the DNA checkpoint kinase Chk1, and to synergize with genotoxic agents. USP7, known as herpes-associated-ubiquitin-specificprotease (HAUSP), is a deubiquitylating enzyme that regulates the levels of the oncoprotein HDM2 and its substrate, the tumor suppressor p53. P005091 accelerated the degradation of HDM2, while analogs of the compound induced dose- and time-dependent increases in the protein levels of p53 and p21.What’s more,P005091 induced apoptosis in numerous cancer cell lines, including both p53+/+ and p53-mutant cancer cell lines.
Reference
Jeffrey G Marblestone. Ubiquitin Drug Discovery & Diagnostics 2009 – First Annual Conference. IDrugs. 2009; 12(12):750 – 753.
- 1. Letizia Granieri, Federica Marocchi, et al. "Targeting the USP7/RRM2 axis drives senescence and sensitizes melanoma cells to HDAC/LSD1 inhibitors." Cell Rep. 2022 Sep 20;40(12):111396. PMID: 36130505
- 2. Lee MJ, Miller Z, et al. "H727 cells are inherently resistant to the proteasome inhibitor carfilzomib, yet require proteasome activity for cell survival and growth." Sci Rep. 2019 Mar 11;9(1):4089. PMID: 30858500
| Physical Appearance | A solid |
| Storage | Store at 4°C |
| M.Wt | 348.22 |
| Cas No. | 882257-11-6 |
| Formula | C12H7Cl2NO3S2 |
| Synonyms | P005091,P5091 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥17.4 mg/mL in DMSO |
| Chemical Name | 1-[5-(2,3-dichlorophenyl)sulfanyl-4-nitrothiophen-2-yl]ethanone |
| SDF | Download SDF |
| Canonical SMILES | CC(=O)C1=CC(=C(S1)SC2=C(C(=CC=C2)Cl)Cl)[N+](=O)[O-] |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
NCI-60 human tumor cell line. |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
Growth inhibition: 48 h. Cytotoxic activity: 72 h.Solubilized in 100% (v/v) DMSO at 400-fold the desired final maximum test concentration and stored frozen prior to use. |
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Applications |
P005091 exhibits growth inhibition with GI50 value of 1.82 μM in HL-60(TB) cell line and exhibits broad growth inhibition. In HCT-116 cells, P005091 shows cytotoxic activity with EC50 value of 9.21 μM. |
| Animal experiment [1]: | |
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Animal models |
Severe combined immunodeficient (SCID) mice inoculated subcutaneously with human multiple myeloma tumor cells. |
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Dosage form |
10 mg/kg; intravenously twice a week for three weeks. |
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Applications |
In SCID mice, P5091 significantly inhibits human plasmacytoma growth and enhances survival. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Cao P, Weinstock J, Kingsbury WD, et al. Anti-neoplastic compounds, compositions and methods. Patent: US 8680139 B2, 2009. |
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| Description | P5091(P005091) is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with EC50 of 4.2 μM and the closely related USP47. | |||||
| Targets | ||||||
| IC50 | 4.2 μM (EC50) | |||||
Quality Control & MSDS
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Chemical structure
Related Biological Data
Related Biological Data
