P5091

製品コードS7132 バッチS713201

印刷

化学情報

Chemical Structure 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
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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. This compound exhibits potent, specific, and selective deubiquitylating activity against USP7. In contrast, it does not inhibit other DUBs or other families of cysteine proteases tested (EC50 > 100 mM). This chemical 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 this compound. Moreover, it inhibits USP7- but not USP2- or USP8-mediated cleavage of poly K48-linked ubiquitin chains. USP7 inhibition by this compound induces HDM2 polyubiquitylation and accelerates degradation of HDM2. It inhibits USP7 deubiquitylating activity, without blocking proteasome activity in MM Cells.  This chemical induces a dose-dependent decrease in viability of various MM cell lines. It overcomes bone marrow stromal cell-induced growth of MM Cells. This compound decreased HDM2 and HDMX, as well as upregulated p53 and p21 levels. Overall, this compound-induced cytotoxicity is mediated in part via HDM2-p21 signaling axis and although p53 is upregulated in response to this chemical treatment, the cytotoxic activity of it is not dependent on p53. [1]
in vivo

In animal tumor model studies, P5091 is well tolerated, inhibits tumor growth, and prolongs survival. Combining this compound with HDAC inhibitor SAHA 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 P5091 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

  • https://pubmed.ncbi.nlm.nih.gov/22975377/
  • https://pubmed.ncbi.nlm.nih.gov/24900381/
  • https://pubmed.ncbi.nlm.nih.gov/35061527/

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：

ACC1 is a dual metabolic-epigenetic regulator of Treg stability and immune tolerance [ Mol Metab, 2025, 94:102111] PubMed: 39929287
The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression [ Neoplasia, 2025, 66:101192] PubMed: 40472738
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
USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder [ Nat Commun, 2023, 14(1):8481] PubMed: 38123574
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

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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