1. Cell Cycle/DNA Damage
  2. Deubiquitinase
  3. P005091

P005091 (Synonyms: P5091)

Cat. No.: HY-15667 Purity: 99.94%
Handling Instructions

P005091 is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with an EC50 of 4.2 μM.

For research use only. We do not sell to patients.

P005091 Chemical Structure

P005091 Chemical Structure

CAS No. : 882257-11-6

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 79 In-stock
Estimated Time of Arrival: December 31
5 mg USD 72 In-stock
Estimated Time of Arrival: December 31
10 mg USD 96 In-stock
Estimated Time of Arrival: December 31
50 mg USD 300 In-stock
Estimated Time of Arrival: December 31
100 mg USD 480 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Top Publications Citing Use of Products

    P005091 purchased from MCE. Usage Cited in: Mol Carcinog. 2019 Jan;58(1):42-54.

    Treatment with P5091 increases the cleavage of CASP9, CASP3, and PARP. ESCC cells Kyse450, Kyse510 and Kyse30 are treated with P5091 for 72 h and cell lysates are assessed by western blotting with specific antibodies against cleaved CASP9, CASP3, or PARP. GAPDH is used as a control.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    P005091 is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with an EC50 of 4.2 μM.

    IC50 & Target

    EC50: 4.2 μM (USP7)

    In Vitro

    P005091 is a trisubstituted thiophene with dichlorophenylthio, nitro, and acetyl substituents mediating anti-USP7 activity. P005091 exhibits potent, specific, and selective deubiquitylating activity against USP7. In contrast, P005091 does not inhibit other DUBs or other families of cysteine proteases tested (EC50 > 100 mM). P005091 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 P005091. Moreover, P005091 inhibits USP7- but not USP2- or USP8-mediated cleavage of poly K48-linked ubiquitin chains. USP7 inhibition by P005091 induces HDM2 polyubiquitylation and accelerates degradation of HDM2. P005091 inhibits USP7 deubiquitylating activity, without blocking proteasome activity in MM Cells. P005091 inhibits growth in MM cells and overcomes bortezomib-resistance. P005091 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). P005091 overcomes bone marrow stromal cell-induced growth of MM Cells. P005091 decreases HDM2 and HDMX, as well as upregulated p53 and p21 levels. Overall, P005091-induced cytotoxicity is mediated in part via HDM2-p21 signaling axis and although p53 is upregulated in response to P005091 treatment, the cytotoxic activity of P005091 is not dependent on p53[1].

    In Vivo

    In animal tumor model studies, P005091 is well tolerated, inhibits tumor growth, and prolongs survival. Combining P005091 with lenalidomide, HDAC inhibitor SAHA, or dexamethasone triggers synergistic anti-MM activity[1].

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 50 mg/mL (143.59 mM; Need ultrasonic)

    H2O : < 0.1 mg/mL (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 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
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: 2.5 mg/mL (7.18 mM); Suspended solution; Need ultrasonic and warming

    • 2.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (7.18 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Kinase Assay
    [1]

    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.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    For the animal study, P005091 is dissolved in 4% NMP(N-methyl-2-Pyrrolidone), 4% Tween-80, and 92% Milli-Q water at a final concentration of 2 mg/mL. The human plasmacytoma xenograft model is performed as previously described. CB-17 SCID-mice are subcutaneously inoculated with MM.1S, ARP-1, or RPMI-8226 cells in 100 μL of serum free RPMI-1640 medium. When tumors are measurable (100-180 mm3), mice are randomized into treatment groups. In the SCID-hu model, human fetal bone grafts are subcutaneously implanted into SCID mice. Four weeks after bone implantation, INA-6 cells are injected directly into the fetal bone implant in SCID mice; and as a measure of tumor burden, mouse sera samples are analyzed for shIL-6R by ELISA. Upon detection of shIL-6R, mice are treated with vehicle or P005091, and mouse serum is analyzed for alterations in shIL-6R levels.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    348.22

    Formula

    C₁₂H₇Cl₂NO₃S₂

    CAS No.

    882257-11-6

    SMILES

    CC(C1=CC([N+]([O-])=O)=C(SC2=CC=CC(Cl)=C2Cl)S1)=O

    Shipping

    Room temperature in continental US; may vary elsewhere

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    Product Name:
    P005091
    Cat. No.:
    HY-15667
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    Cat. No.: HY-15667