P5091 (P005091)

Alias: P005091; P-005091; P 005091; P5091; P-5091; P 5091.
Cat No.:V1323 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.
P5091 (P005091) Chemical Structure CAS No.: 882257-11-6
Product category: DUB
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

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.

Biological Activity I Assay Protocols (From Reference)
Targets
USP7(EC50= 4.2 μM)
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.
ln Vivo
In animal tumor model studies, P5091 is well tolerated, inhibits tumor growth, and prolongs survival. Combining P5091 with lenalidomide, HDAC inhibitor SAHA, or dexamethasone triggers synergistic anti-MM activity.
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.
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.
Animal Protocol
10 mg/kg; injected intravenously
Severe combined immunodeficient (SCID) mice inoculated subcutaneously with human multiple myeloma tumor cells.
References

[1].A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance. Cancer Cell. 2012 Sep 11;22(3):345-58.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C12H7CL2NO3S2
Molecular Weight
348.22
Exact Mass
346.92
Elemental Analysis
C, 41.39; H, 2.03; Cl, 20.36; N, 4.02; O, 13.78; S, 18.42
CAS #
882257-11-6
Appearance
Solid powder
SMILES
CC(C1=CC([N+]([O-])=O)=C(SC2=CC=CC(Cl)=C2Cl)S1)=O
InChi Key
LKZLGMAAKNEGCH-UHFFFAOYSA-N
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
Chemical Name
1-(5-((2,3-dichlorophenyl)thio)-4-nitrothiophen-2-yl)ethanone
Synonyms
P005091; P-005091; P 005091; P5091; P-5091; P 5091.
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : 25~28 mg/mL ( 71.79~80.4 mM)
1-Methyl-2-pyrrolidinone : ~100 mg/mL (~287.17 mM)
Solubility (In Vivo)
6.5% DMSO+40% PEG300+5% Tween80+48.5% ddH2O: 1.95mg/ml (Please use freshly prepared in vivo formulations for optimal results.)
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.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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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.
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Biological Data
  • P5091 (P005091)

  • P5091 (P005091)

    P5091 inhibits xenografted human MM cell growth, prolongs survival, and blocks angiogenesis in CB-17 mice. Cancer Cell. 2012 Sep 11;22(3):345-58.
  • P5091 (P005091)

    P5091 inhibits USP7 activity, induces MM cell death, and overcomes bortezomib-resistance. Cancer Cell. 2012 Sep 11;22(3):345-58.
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