P5091 (P005091) 882257-11-6

.cp_wz table {border-top: 1px solid #ccc;border-left:1px solid #ccc; } .cp_wz table td{border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc;border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;}


Molecular Weight: 348.22 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.


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.


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.

Protocol(Only for Reference)

Kinase Assay: [1]

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.

Animal Study: [1]

Animal Models	CB-17 SCID-mice
Formulation	4% NMP (N-methyl-2-Pyrrolidone), 4% Tween-80, and 92% Milli-Q water
Dosages	10 mg/kg
Administration
Solubility	30% PEG400/0.5% Tween80/5% propylene glycol, pH 4, 10 mg/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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Baboon	Dog	Monkey	Rabbit	Guinea pig	Rat	Hamster	Mouse
Weight (kg)	12	10	3	1.8	0.4	0.15	0.08	0.02
Body Surface Area (m2)	0.6	0.5	0.24	0.15	0.05	0.025	0.02	0.007
Km factor	20	20	12	12	8	6	5	3

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×	mouse Km(3)	= 11.2 mg/kg
	rat Km(6)

Chemical Information

Molecular Weight (MW)	348.22
Formula	C12H7Cl2NO3S2
CAS No.	882257-11-6

Storage	3 years -20℃Powder
	6 months-80℃in solvent (DMSO, water, etc.)
Synonyms

Solubility (25°C) *	In vitro	DMSO	28 mg/mL (80.4 mM)
		Water	<1 mg/mL (
		Ethanol	<1 mg/mL (
	In vivo	30% PEG400/0.5% Tween80/5% propylene glycol, pH 4	10 mg/mL

Chemical Name	Ethanone, 1-[5-[(2,3-dichlorophenyl)thio]-4-nitro-2-thienyl]-

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.34822	3.4822	6.9644	10.4466

Contact us if you need more details on P5091 882257-11-6. We are ready to answer your questions on packaging, logistics, certification or any other aspects about P005091 882257-11-6、882257-11-6. If these products fail to match your need, please contact us and we would like to provide relevant information.

Product Categories : Ubiquitin > DUB Inhibitor