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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
P5091 (also called P5091; P-005091; P-5091; P005091) is a novel, potent, specific and selective inhibitor of ubiquitin-specific protease 7 (USP7) with potential anticancer activity. It inhibits USP7 with an EC50 of 4.2 μM and exhibits little effects against the closely related USP47. 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. In addition, P005091 induced apoptosis in numerous cancer cell lines, including both p53+/+ and p53-mutant cancer cell lines.
| Targets |
USP7(EC50= 4.2 μM)
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| ln Vitro |
P5091 is a trisubstituted thiophene with dichlorophenylthio, nitro, and acetyl substituents mediating anti-USP7 activity. P5091 exhibits potent, specific, and selective deubiquitylating activity against USP7. In contrast, P5091 does not inhibit other DUBs or other families of cysteine proteases tested (EC50 > 100 mM). P5091 inhibits the labeling of USP7 with HA-UbVME in a concentration-dependent manner. USP7-mediated cleavage of high molecular weight polyubiquitin chains is inhibited in a dose-dependent manner by P5091. Moreover, P5091 inhibits USP7- but not USP2- or USP8-mediated cleavage of poly K48-linked ubiquitin chains. USP7 inhibition by P5091 induces HDM2 polyubiquitylation and accelerates degradation of HDM2. P5091 inhibits USP7 deubiquitylating activity, without blocking proteasome activity in MM Cells. P5091 inhibits growth in MM cells and overcomes bortezomib-resistance. P5091 induces a dose-dependent decrease in viability of various MM cell lines, including those that are resistant to conventional therapies dexamethasone (Dex) (MM.1R), doxorubicin (Dox-40), or melphalan (LR5) (IC50 range 6–14 μM). P5091 overcomes bone marrow stromal cell-induced growth of MM Cells. P5091 decreased HDM2 and HDMX, as well as upregulated p53 and p21 levels. Overall, P5091-induced cytotoxicity is mediated in part via HDM2-p21 signaling axis and although p53 is upregulated in response to P5091 treatment, the cytotoxic activity of P5091 is not dependent on p53.
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| ln Vivo |
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| Enzyme Assay |
Recombinant enzymes in 20 mM Tris-HCl (pH 8.0), 2 mM CaCl2, and 2 mM β-mercaptoethanol are incubated with dose ranges of P005091 for 30 min in a 96-well plate before the addition of Ub-PLA2 and NBD C6-HPC or Ub-EKL and EKL substrate. The liberation of a fluorescent product within the linear range of the assay is monitored using a Perkin Elmer Envision fluorescence plate reader. Vehicle (2% [v/v] DMSO) and 10 mM N-ethylmaleimide (NEM) are included as controls.
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| Cell Assay |
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.
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| Animal Protocol |
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| References |
| Molecular Formula |
C12H7CL2NO3S2
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| Molecular Weight |
348.22
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| Exact Mass |
346.924
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| Elemental Analysis |
C, 41.39; H, 2.03; Cl, 20.36; N, 4.02; O, 13.78; S, 18.42
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| CAS # |
882257-11-6
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| Related CAS # |
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| PubChem CID |
2819993
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
452.4±45.0 °C at 760 mmHg
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| Flash Point |
227.4±28.7 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.685
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| LogP |
5.02
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
393
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C)C1=CC([N+](=O)[O-])=C(SC2C(Cl)=C(Cl)C=CC=2)S1
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| InChi Key |
LKZLGMAAKNEGCH-UHFFFAOYSA-N
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| InChi Code |
1-(5-((2,3-dichlorophenyl)thio)-4-nitrothiophen-2-yl)ethanone InChI=1S/C12H7Cl2NO3S2/c1-6(16)10-5-8(15(17)18)12(20-10)19-9-4-2-3-7(13)11(9)14/h2-5H,1H3
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| Chemical Name |
1-(5-((2,3-dichlorophenyl)thio)-4-nitrothiophen-2-yl)ethanone
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| Synonyms |
P005091; P-005091; P 005091; P5091; P-5091; P 5091.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 25~28 mg/mL ( 71.79~80.4 mM)
1-Methyl-2-pyrrolidinone : ~100 mg/mL (~287.17 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 8 mg/mL (22.97 mM) in 4% NMP 3% Tween80 + 20% PEG400 73% ddH2O (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Solubility in Formulation 2: 2.5 mg/mL (7.18 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 6.5% DMSO+40% PEG300+5% Tween80+48.5% ddH2O: 1.95mg/ml |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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