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P005091 (P5091) is a cell permeable, potent and specific inhibitor of deubiquitylating enzyme USP7 with an EC50 of 4.2 μM, which induces elevated p53 and apoptosis in cancer cell lines. 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-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. P005091 induces HDM2 polyubiquitylation and accelerates degradation of HDM2.
P005091 displays antiangiogenic activity in vivo. P005091 is well tolerated, inhibits tumor growth and prolongs survival in animal models of cancer.
Cell Death Differ. 2026 Jan 31; .
Targeting the USP7-PRMT6 epigenetic axis overcomes chemoresistance in breast cancer by coordinating H3R2me2a deposition and RNF168 methylation for DNA
P005091 purchased from AbMole
Chem Biol Interact. 2025 Aug 06; .
Cigarette smoke-induced glycerophospholipid DLPC promotes macrophage ferroptosis through the USP7/GPX4 regulatory axis in chronic obstructive pulmonary disease
P005091 purchased from AbMole
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Source | Int J Mol Sci (2017). Figure 3. P5091 |
| Method | cell proliferation assay | |
| Cell Lines | ovarian cancer cell | |
| Concentrations | 50 μM | |
| Incubation Time | 12 and 24 h | |
| Results | At 12 and 24 hours, control cells treated with DMSO propagated healthily, while the growth of P5091 treated HeyA8 and OVCAR-8 cells was remarkably repressed, with some cells exhibiting rounded shapes or even detaching from the culture dish, indicative of cell death |
| Molecular Weight | 348.22 |
| Formula | C12H7Cl2NO3S2 |
| CAS Number | 882257-11-6 |
| Solubility (25°C) | DMSO 24 mg/mL N-Methylpyrrolidone (NMP): 80 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related Deubiquitinase Products |
|---|
| P22077
P22077 is a selective inhibitor of ubiquitin-specific protease (USP) 7 with EC50 of 8.6 μM. P 22077 also inhibits USP47 with an EC50 of 8.74 μM. |
| b-AP15
b-AP15 is a deubiquitinases inhibitor for 19S proteasomes activity of Ub-AMC cleavage with IC50 of 2.1 μM. *The compound is unstable in solutions, freshly prepared is recommended |
| PR-619
PR-619 is a broad-spectrum reversible DUB (deubiquitinating enzyme) inhibitor of USP2, USP4, USP5, USP7 and USP8 with an EC50 of 3-9 μM. PR-619 also induces endoplasmic reticulum stress and endoplasmic reticulum stress-associated apoptosis. |
| LDN-57444
LDN-57444 is a reversible, competitive proteasome inhibitor for Uch-L1 with IC50 of 0.88 μM, 28-fold selectivity over isoform Uch-L3. |
| TCID
TCID is a DUB inhibitor for ubiquitin C-terminal hydrolase L3 with IC50 of 0.6 μM, 125-fold selective to L1. |
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