| Name | P005091 |
| Description | P005091 (P5091) is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with EC50 of 4.2 μM. |
| Kinase 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. |
| Animal Research | Animal Models: 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. Formulation: 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. |
| In vitro | P5091 demonstrates synergistic anti-multiple myeloma (anti-MM) activity when used in combination with Lenalidomide, the HDAC inhibitor SAHA, or Dexamethasone. In animal tumor models, P5091 is well-tolerated, inhibits tumor growth, and prolongs survival. |
| In vivo | P5091 exhibits potent, specific, and selective deubiquitinating (deubiquitinase) activity against USP7. Conversely, P5091 does not inhibit other tested DUBs or proteases from different families (EC50 >100 mM). It decreases HDM2 and HDMX levels while upregulating p53 and p21. P5091-induced cytotoxicity is partly mediated via the HDM2-p21 signaling axis, and despite the upregulation of p53 following P5091 treatment, its cytotoxic effects do not depend on p53. P5091 concentration-dependently inhibits USP7 tagged with HA-UbVME and dose-dependently inhibits USP7-mediated disassembly of ultra-high molecular weight ubiquitin chains. Moreover, P5091 inhibits the breakdown of polyK48-linked ubiquitin chains specifically by USP7 rather than USP2 or USP8. It suppresses USP7 deubiquitinase activity in MM cells without inhibiting protease activities and overcomes bone marrow stromal cell-induced MM cell growth. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 68 mg/mL, Sonication is recommended.
|
| Keywords | inhibit | P 5091 | Deubiquitinase | P005091 | P-5091 | P 005091 | DUBs | Inhibitor | P-005091 |
| Inhibitors Related | P22074 | BAY 11-7082 | USP15-IN-1 | N-Ethylmaleimide | DUB-IN-1 | SJB3-019A | USP30 inhibitor 11 | Vialinin A | GRL0617 | Spautin-1 | 6-Thioguanine | USP8-IN-3 |
| Related Compound Libraries | DNA Damage & Repair Compound Library | Target-Focused Phenotypic Screening Library | Bioactive Compound Library | Autophagy Compound Library | Inhibitor Library | NO PAINS Compound Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Cell Cycle Compound Library | Anti-Cancer Active Compound Library |
United States
