P22077

製品コードS7133 バッチS713302

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₂H₇F₂NO₃S₂
	分子量	315.32	CAS No.	1247819-59-5
Solubility (25°C)*	体外	DMSO	63 mg/mL (199.79 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	P22077 is an inhibitor of ubiquitin-specific protease USP7 with EC50 of 8.6 μM, also inhibits the closely related USP47.
in vitro	P22077 is an analog of the recently discovered USP7 inhibitor P5091. This compound 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 this chemical in vitro against a panel of DUBs, cysteine proteases, and other families of proteolytic enzymes demonstrate that it inhibits USP7 and the closely related DUB USP47. It inhibits a smaller subset of DUBs at a concentration of 15–45 mM in cell lysates. This compound induces (tumor) cell death with EC50 values in the low micromolar range. Its inhibition exhibited changes in ubiquitylated protein levels that are distinct from the broad specificity inhibitor. 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 this chemical. ^[2]
in vivo	Inhibition of USP7 by P22077 also inhibits melanoma tumour growth in vivo.

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.

in vitro

P22077 is an analog of the recently discovered USP7 inhibitor P5091. This compound 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 this chemical in vitro against a panel of DUBs, cysteine proteases, and other families of proteolytic enzymes demonstrate that it inhibits USP7 and the closely related DUB USP47. It inhibits a smaller subset of DUBs at a concentration of 15–45 mM in cell lysates. This compound induces (tumor) cell death with EC50 values in the low micromolar range. Its inhibition exhibited changes in ubiquitylated protein levels that are distinct from the broad specificity inhibitor. 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 this chemical. ^[2]

in vivo

Inhibition of USP7 by P22077 also inhibits melanoma tumour growth in vivo.

プロトコル(参考用のみ)

キナーゼアッセイ	UbL-EKL assays
キナーゼアッセイ	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.

参考

https://pubmed.ncbi.nlm.nih.gov/21133675/
https://pubmed.ncbi.nlm.nih.gov/22118674/
https://pubmed.ncbi.nlm.nih.gov/34469054/

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：

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
Oxyberberine sensitizes liver cancer cells to sorafenib via inhibiting NOTCH1-USP7-c-Myc pathway [ Hepatol Commun, 2024, 8(4)e0405]	PubMed: 38573832
Identification of Novel Therapeutic Strategies for Immune-Active Oesophageal Adenocarcinoma [ Queen's University Belfast, 2023, ]	PubMed: None
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

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。