P005091 is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with EC50 of 4.2 μM and the closely related USP47.

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 HCT-116 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.

IU1

Lactacystin

MLN 4924

​NSC 632839​ 

PR-619 

(R)-MG132

(S)-MG132

WP1130

HBX 19818

ML-323 

P 22077  

PR-619  

SJB2-043  

SJB3-019A