受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C12H7F2NO3S2 |
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分子量 | 315.32 | CAS No. | 1247819-59-5 | ||||
Solubility (25°C)* | 体外 | DMSO | 63 mg/mL (199.79 mM) | ||||
Ethanol | 1 mg/mL (3.17 mM) | ||||||
Water | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | P22077 is an inhibitor of ubiquitin-specific protease USP7 with EC50 of 8.6 μM, also inhibits the closely related USP47. |
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in vitro | P22077 is an analog of the recently discovered USP7 inhibitor P5091. P22077 has negligible activity versus DEN1 and SENP2core over the concentration range tested, but inhibits USP7 with an IC50 of 8 μM. [1] The inhibitory activities of P22077 in vitro against a panel of DUBs, cysteine proteases, and other families of proteolytic enzymes demonstrate that P22077 inhibits USP7 and the closely related DUB USP47. P22077 inhibits a smaller subset of DUBs at a concentration of 15–45 mM in cell lysates. P22077 induces (tumor) cell death with EC50 values in the low micromolar range. P22077 inhibition exhibited changes in ubiquitylated protein levels that are distinct from the broad specificity inhibitor. P22077 treatment of U2OS cells during release from G1/S arrest induces with hydroxyurea resulted in a dose-dependent loss of claspin protein and a concomitant decrease in phospho Serine 317 Chk1. Furthermore, quantitative MS suggestes the E3 ubiquitin ligase components RBX1, DCAF7, DCAF11, and the DNA damage binding protein 1 (DDB1) to be reduced upon cellular treatment with P22077. [2] |
in vivo | Inhibition of USP7 by P22077 also inhibits melanoma tumour growth in vivo. |
キナーゼアッセイ | UbL-EKL assays | |
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Unless stated otherwise, recombinant isopeptidase is mixed with UbL-EKL and EKLsubstrate I to final concentrations of 20, 50, and 20 nM, respectively, in a total volume of 100 μL in a well in a black-walled 96-well plate. All dilutions are performed in isopeptidase assay buffer (20 mM Tris-HCl, pH 8.0, 2 mM CaCl2, and 2 mM β-mercaptoethanol). The increase in fluorescence intensity over time is determined on a Perkin Elmer Envision fluorescence plate reader with excitation and emission filters corresponding to the fluorescence resonance energy transfer peptide utilized. Unless stated otherwise, net relative fluorescence units (RFUs) are determined by subtracting the blank RFU value (20 nM EKL substrate I or 100 nM EKL substrate II in isopeptidase assay buffer) from each data point. SENP2core, SUMO3-EKL sensitivity experiments are performed by mixing 0–100 fM SENP2core with 50 nM SUMO3-EKL, and 100 nM EKL substrate I in a total volume of 100 μL as above. | ||
細胞アッセイ | 細胞株 | Cell-free assays |
濃度 | 8 μM | |
反応時間 | ||
実験の流れ | ||
動物実験 | 動物モデル | Female SD nude mice |
投薬量 | 10 mg/kg | |
投与方法 | i.v. |
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ER Stress-Activated HSF1 Governs Cancer Cell Resistance to USP7 Inhibitor-Based Chemotherapy through the PERK Pathway [ Int J Mol Sci, 2024, 25(5)2768] | PubMed: 38474017 |
Functional skewing of TRIM21-SIRT5 interplay dictates IL-1β production in DSS-induced colitis [ EMBO Rep, 2022, e54391] | PubMed: 35770730 |
Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice [ Front Pharmacol, 2022, 13:1021361] | PubMed: 36386139 |
Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice [ Front Pharmacol, 2022, 13:1021361] | PubMed: 36386139 |
USP7 sustains an active epigenetic program via stabilizing MLL2 and WDR5 in diffuse large B-cell lymphoma [ Cell Biochem Funct, 2022, 10.1002/cbf.3702] | PubMed: 35411950 |
Targeting USP47 overcomes tyrosine kinase inhibitor resistance and eradicates leukemia stem/progenitor cells in chronic myelogenous leukemia [ Nat Commun, 2021, 12(1):51] | PubMed: 33397955 |
USP47-Mediated Deubiquitination and Stabilization of TCEA3 Attenuates Pyroptosis and Apoptosis of Colorectal Cancer Cells Induced by Chemotherapeutic Doxorubicin [ Front Pharmacol, 2021, 12:713322] | PubMed: 34630087 |
Pharmacological inhibition of USP7 suppresses growth and metastasis of melanoma cells in vitro and in vivo [ J Cell Mol Med, 2021, 25(19):9228-9240] | PubMed: 34469054 |
The occurrence of lupus nephritis is regulated by USP7-mediated JMJD3 stabilization [ Immunol Lett, 2021, S0165-2478(21)00064-X] | PubMed: 33895173 |
The role of USP7 in the Shoc2 - ERK1/2 signaling axis and Noonan-like syndrome with loose anagen hair (NSLAH) [ J Cell Sci, 2021, jcs.258922] | PubMed: 34553755 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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