P005091

P005091

CAT N°: 15224
Price:

99.00 84.15

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 ?M, respectively) with little activity against other classes of proteases, including caspases, cathepsins, calpain, metalloproteases, and serine proteases (EC50s = > 100 ?M).{24461,24462} P005091 has been shown to accelerate the degradation of the USP7 substrate HDM2 in several multiple myeloma cell lines (EC50 = 11 ?M) and to inhibit the growth of HCT116 human colorectal cancer cells (EC50 = 11 ?M) synergistically with doxorubicin, etoposide, or mechlorethamine.{24461} In vivo, 10 mg/kg P005091 prolongs survival and reduces tumor growth in mice bearing human multiple myeloma and B cell leukemia xenografts.{24461}

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