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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.Formal Name: 1-[5-[(2,3-dichlorophenyl)thio]-4-nitro-2-thienyl]-ethanone. CAS Number: 882257-11-6. Synonyms: P5091. Molecular Formula: C12H7Cl2NO3S2. Formula Weight: 348.2. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 3 mg/ml, DMF:PBS(pH7.2) (1:2): 0.3 mg/ml, DMSO: 0.2 mg/ml. lambdamax: 268, 318 nm. SMILES: ClC1=C(Cl)C(SC2=C([N+]([O-])=O)C=C(C(C)=O)S2)=CC=C1. InChi Code: 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. InChi Key: LKZLGMAAKNEGCH-UHFFFAOYSA-N.
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