P5091

• CAT Number: I005302
• CAS Number: 882257-11-6
• Molecular Formula: C₁₂H₇Cl₂NO₃S₂
• Molecular Weight: 348.22
• Purity: ≥95%
• Synonyms: P005091; 1-[5-(2,3-dichlorophenyl)sulfanyl-4-nitrothiophen-2-yl]ethanone
• Target: DUB
• Solubility: DMSO: 28 mg/mL, H2O: <1 mg/mL
• Storage: Store at 4°C
• IC50: 4.2 uM (EC50)
• InChI: InChI=1S/C12H7Cl2NO3S2/c1-6(16)10-5-8(15(17)18)12(20-10)19-9-4-2-3-7(13)11(9)14/h2-5H,1H3
• InChIKey: LKZLGMAAKNEGCH-UHFFFAOYSA-N
• SMILES: CC(=O)C1=CC(=C(S1)SC2=C(C(=CC=C2)Cl)Cl)[N+](=O)[O-]

P005091(cas# 882257-11-6) is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with EC50 of 4.2 μM.
IC50 Value: 4.2 uM (EC50).


Ubiquitin-specific proteases (USP/UBP) remove ubiquitin from proteins, sparing them from degradation by the proteasome. USP7 is a cysteine protease associated with prostate cancer that selectively deubiquitylates HDM2, the ubiquitin E3 ligase for the tumor suppressor p53. P005091 is a trisubstituted thiophene that inhibits USP7 and the closely related USP47 (EC50s = 4.2 and 4.3 μM, respectively) with little activity against other classes of proteases, including caspases, cathepsins, calpain, metalloproteases, and serine proteases (EC50s = > 100 μM). P005091 has been shown to accelerate the degradation of the USP7 substrate HDM2 in several multiple myeloma cell lines (EC50 = 11 μM) and to inhibit the growth of HCT116 human colorectal cancer cells (EC50 = 11 μM) synergistically with doxorubicin, etoposide, or mechlorethamine. In vivo, 10 mg/kg P005091 prolongs survival and reduces tumor growth in mice bearing human multiple myeloma and B cell leukemia xenografts.

Reference

1. Cell Biochem Biophys. 2011 Jun;60(1-2):61-8. doi: 10.1007/s12013-011-9185-5.

The multifaceted roles of USP7: new therapeutic opportunities.

Nicholson B(1), Suresh Kumar KG.

Author information:
(1)Progenra Inc, 277 Great Valley Parkway, Malvern, PA 19355, USA.


The deubiquitylating enzyme USP7 (HAUSP) sits at a critical node regulating the
activities of numerous proteins broadly characterized as tumor suppressors, DNA
repair proteins, immune responders, viral proteins, and epigenetic modulators.
Aberrant USP7 activity may promote oncogenesis and viral disease making it a
compelling target for therapeutic intervention. Disclosed drug discovery programs
have identified inhibitors of USP7 such as P005091 with cellular proof of concept
and anti-proliferative activity in cancer models. Taken together, USP7 inhibitors
hold promise as a new strategy for the treatment of disease.