Home Ubiquitin DUB inhibitor P5091 For research use only.

P5091

Synonyms: P005091

P5091 is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with EC50 of 4.2 μM and the closely related USP47.

P5091 Chemical Structure

P5091 Chemical Structure

CAS: 882257-11-6

Selleck's P5091 has been cited by 53 publications

Purity & Quality Control

Batch: Purity: 99.91%
99.91

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Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Sf9 cells Function assay Inhibition of recombinant USP7 expressed in Sf9 cells by Ub-CHOP reporter assay, EC50=4.2 μM 24900381
human HCT116 cells Cytotoxic assay 72 h Cytotoxicity against human HCT116 cells after 72 hrs, EC50=11 μM 24900381
multiple myeloma cells Function assay Inhibition of USP7 in multiple myeloma cells (unknown origin) by immunohistochemistry, EC50 = 4.2 μM. 25364867
Sf9 Function assay 30 mins Inhibition of full-length recombinant USP7 (unknown origin) expressed in Sf9 cells using Ub-EKL as substrate preincubated for 30 mins followed by substrate addition by fluorescence based assay, IC50 = 4.2 μM. 28768102
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Biological Activity

Description P5091 is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with EC50 of 4.2 μM and the closely related USP47.
Targets
USP7 [1]
(Cell-free assay)		 USP47 [2]
(Cell-free assay)
4.2 μM(EC50) 4.3 μM
In vitro
In 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. [1]
Kinase Assay Ubiquitin Protease Assays
Recombinant enzymes in 20 mM Tris-HCl (pH 8.0), 2 mM CaCl2, and 2 mM β-mercaptoethanol are incubated with dose ranges of P5091 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 Research Cell lines 293T cells
Concentrations 10 μM
Incubation Time 24 h
Method

Cells were treated with indicated concentration of drug for 24 h.
Experimental Result Images Methods Biomarkers Images PMID
Western blot HAUSP / N-Myc USP7 / p53 / p21 29616860
Immunofluorescence PTEN 28418900
Growth inhibition assay Cell viability 30045945
In Vivo
In 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. [1]
Animal Research Animal Models CB-17 SCID-mice
Dosages 10 mg/kg
Administration --

Chemical lnformation & Solubility

Molecular Weight 348.22 Formula

C12H7Cl2NO3S2
CAS No. 882257-11-6 SDF Download P5091 SDF
Smiles CC(=O)C1=CC(=C(S1)SC2=C(C(=CC=C2)Cl)Cl)[N+](=O)[O-]
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 28 mg/mL ( (80.4 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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