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P5091 (P005091)

Name: P5091 (P005091)
Brand: Selleck Chemicals
SKU: S7132
Rating: 5 (36 reviews)

Catalog No.S7132

For research use only.

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.

CAS No. 882257-11-6

Selleck's P5091 (P005091) has been cited by 36 publications

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DUB Signaling Pathway Map

Biological Activity

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

USP7 ^[1] (Cell-free assay)	USP47 ^[2] (Cell-free assay)
4.2 μM(EC50)	4.3 μM

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]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

Sf9 cells	NV7P[HY{TnWwY4Tpc44h[XO\|YYm=		M33EfGlvcGmkaYTpc44hd2ZicnXjc41jcW6jboSgWXNRPyCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJIJ6KFWkLVPIU3AhemWyb4L0[ZIh[XO\|YYmsJGVEPTB;ND6yJO69VQ>?	NXnCW4EzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA{QDFpPkK0PVAxOzhzPD;hQi=>
human HCT116 cells	MVfDfZRwfG:6aXRCpIF{e2G7	NUHXcVk{PzJiaB?=	NVficYFQS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUEOWMUG2JINmdGy\|IHHmeIVzKDd{IHjyd{whTUN3ME2xNUDPxE1?	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMEO4NUc,OjR7MECzPFE9N2F-
multiple myeloma cells	MWPGeY5kfGmxbjDhd5NigQ>?		MkPQTY5pcWKrdHnvckBw\iCXU2C3JIlvKG23bITpdIxmKG27ZXzvcYEh[2WubIOgLJVvc26xd36gc5Jq\2mwKTDifUBqdW23bn;obZN1d2OqZX3pd5RzgSxiRVO1NEA:KDRwMjFOwG0v	NGf5bm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUO2OFg3Pyd-MkWzOlQ5Pjd:L3G+
Sf9	MU\GeY5kfGmxbjDhd5NigQ>?	MVezNEBucW6\|	MoDTTY5pcWKrdHnvckBw\iCodXzsMYxmdme2aDDy[YNwdWKrbnHueEBWW1B5IDj1cotvd3ewIH;ybYdqdiliZYjwdoV{e2WmIHnuJHNnQSClZXzsd{B2e2mwZzDVZk1GU0xiYYOgd5Vje3S{YYTlJJBz\WmwY4XiZZRm\CCob4KgN\|AhdWmwczDmc4xtd3enZDDifUB{fWK\|dILheIUh[WSmaYTpc44h[nliZnz1c5Jme2OnbnPlJIJie2WmIHHzd4F6NCCLQ{WwJF0hPC5{IN88UU4>	M{nU[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6N{[4NVAzLz5{OEe2PFExOjxxYU6=

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot	HAUSP / N-Myc ; USP7 / p53 / p21	29616860 30045945
Immunofluorescence	PTEN	28418900
Growth inhibition assay	Cell viability	30045945

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]

Protocol (from reference)

Animal Research: ^[1]	Animal Models: CB-17 SCID-mice Dosages: 10 mg/kg Administration: -- (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	28 mg/mL (80.4 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 4% DMSO+30% PEG 400+ddH2O For best results, use promptly after mixing. Click to purchase: PEG400	5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight	348.22
Formula	C₁₂H₇Cl₂NO₃S₂
CAS No.	882257-11-6
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC(=O)C1=CC(=C(S1)SC2=C(C(=CC=C2)Cl)Cl)[N+](=O)[O-]

Download P5091 (P005091) SDF

In vivo Formulation Calculator (Clear solution)

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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