|
受注：045-509-1970 |
技術サポート：[email protected] 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
|
Synonyms | P005091 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C12H7Cl2NO3S2 |
|||
| 分子量 | 348.22 | CAS No. | 882257-11-6 | |
| Solubility (25°C)* | 体外 | DMSO | 28 mg/mL (80.4 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
|
* <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. |
||||
溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | P5091 is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with EC50 of 4.2 μM and the closely related USP47. |
|---|---|
| in vitro | P5091 is a trisubstituted thiophene with dichlorophenylthio, nitro, and acetyl substituents mediating anti-USP7 activity. P5091 exhibits potent, specific, and selective deubiquitylating activity against USP7. In contrast, P5091 does not inhibit other DUBs or other families of cysteine proteases tested (EC50 > 100 mM). P5091 inhibits the labeling of USP7 with HA-UbVME in a concentration-dependent manner. USP7-mediated cleavage of high molecular weight polyubiquitin chains is inhibited in a dose-dependent manner by P5091. Moreover, P5091 inhibits USP7- but not USP2- or USP8-mediated cleavage of poly K48-linked ubiquitin chains. USP7 inhibition by P5091 induces HDM2 polyubiquitylation and accelerates degradation of HDM2. P5091 inhibits USP7 deubiquitylating activity, without blocking proteasome activity in MM Cells. P5091 inhibits growth in MM cells and overcomes bortezomib-resistance. P5091 induces a dose-dependent decrease in viability of various MM cell lines, including those that are resistant to conventional therapies dexamethasone (Dex) (MM.1R), doxorubicin (Dox-40), or melphalan (LR5) (IC50 range 6–14 μM). P5091 overcomes bone marrow stromal cell-induced growth of MM Cells. P5091 decreased HDM2 and HDMX, as well as upregulated p53 and p21 levels. Overall, P5091-induced cytotoxicity is mediated in part via HDM2-p21 signaling axis and although p53 is upregulated in response to P5091 treatment, the cytotoxic activity of P5091 is not dependent on p53. [1] |
| in vivo | In animal tumor model studies, P5091 is well tolerated, inhibits tumor growth, and prolongs survival. Combining P5091 with lenalidomide, HDAC inhibitor SAHA, or dexamethasone triggers synergistic anti-MM activity. [1] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Ubiquitin Protease Assays | |
|---|---|---|
| Recombinant enzymes in 20 mM Tris-HCl (pH 8.0), 2 mM CaCl2, and 2 mM β-mercaptoethanol are incubated with dose ranges of P5091 for 30 min in a 96-well plate before the addition of Ub-PLA2 and NBD C6-HPC or Ub-EKL and EKL substrate. The liberation of a fluorescent product within the linear range of the assay is monitored using a Perkin Elmer Envision fluorescence plate reader. Vehicle (2% [v/v] DMSO) and 10 mM N-ethylmaleimide (NEM) are included as controls. | ||
| 細胞アッセイ | 細胞株 | 293T cells |
| 濃度 | 10 μM | |
| 反応時間 | 24 h | |
| 実験の流れ | Cells were treated with indicated concentration of drug for 24 h. |
|
| 動物実験 | 動物モデル | CB-17 SCID-mice |
| 投薬量 | 10 mg/kg | |
| 投与方法 | -- | |
参考
|
カスタマーフィードバック
-
Data from [Data independently produced by , , Leukemia, 2016, 30(11):2187-2197.]
-
Data from [Data independently produced by , , Leukemia, 2016, 30(11):2187-2197]
-
Data from [Data independently produced by , , Cell Physiol Biochem, 2017, 43(5):1755-1766]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis [ J Exp Clin Cancer Res, 2024, 43(1):28] | PubMed: 38254206 |
| 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 |
| Engineered Microparticles for Treatment of Murine Brain Metastasis by Reprograming Tumor Microenvironment and Inhibiting MAPK Pathway [ Adv Sci (Weinh), 2023, 10(8):e2206212] | PubMed: 36698296 |
| USP7 promotes non-small-cell lung cancer cell glycolysis and survival by stabilizing and activating c-Abl [ Clin Transl Med, 2023, 13(12):e1509] | PubMed: 38082439 |
| De-ubiquitination of SAMHD1 by USP7 promotes DNA damage repair to overcome oncogenic stress and affect chemotherapy sensitivity [ Oncogene, 2023, 42(22):1843-1856] | PubMed: 37081042 |
| Suppression of USP7 negatively regulates the stability of ETS proto-oncogene 2 protein [ Biomed Pharmacother, 2023, 162:114700] | PubMed: 37062218 |
| Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease [ J Transl Med, 2023, 21(1):881] | PubMed: 38057857 |
| USP7 Inhibits Osteoclastogenesis via Dual Effects of Attenuating TRAF6/TAK1 Axis and Stimulating STING Signaling [ Aging Dis, 2023, 14(6):2267-2283] | PubMed: 37199589 |
| USP7 attenuates endoplasmic reticulum stress-induced apoptotic cell death through deubiquitination and stabilization of FBXO7 [ PLoS One, 2023, 18(10):e0290371] | PubMed: 37874827 |
| USP7 attenuates endoplasmic reticulum stress-induced apoptotic cell death through deubiquitination and stabilization of FBXO7 [ PLoS One, 2023, 18(10):e0290371] | PubMed: 37874827 |
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。