P22077

P22077 is a dual inhibitor of the deubiquitylating enzymes ubiquitin-specific protease 7 (USP7) and USP47 (EC50s = 8.01 and 8.74 µM, respectively, in a fluorescence-based enzyme assay). It is selective for USP7 and USP47 over other USPs and proteases with EC50 values greater than 50 µM. P22077 (25 µM) induces the accumulation of polyubiquitinated proteins in HEK293 cells. In neuroblastoma cells in vitro, P22077 blocks deubiquitylation of HDM2, a protein that normally deubiquitinates the tumor suppressor p53 leading to its degradation. When used at concentrations of 10 and 20 µM, it amplifies the cytotoxicity and p53-mediated apoptosis of doxorubicin (Cay-15007) and etoposide (Cay-12092) in neuroblastoma cells. P22077 inhibits tumor growth in neuroblastoma mouse xenograft models when administered at a dose of 20 mg/kg per day.Formal Name: 1-[5-[(2,4-difluorophenyl)thio]-4-nitro-2-thienyl]-ethanone. CAS Number: 1247819-59-5. Molecular Formula: C12H7F2NO3S2. Formula Weight: 315.3. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml, Ethanol: 0.1 mg/ml. lambdamax: 215, 267, 316 nm. SMILES: FC1=CC=C(SC2=C([N+]([O-])=O)C=C(C(C)=O)S2)C(F)=C1. InChi Code: InChI=1S/C12H7F2NO3S2/c1-6(16)11-5-9(15(17)18)12(20-11)19-10-3-2-7(13)4-8(10)14/h2-5H,1H3. InChi Key: RMAMGGNACJHXHO-UHFFFAOYSA-N.