PR-619

製品コードS7130 バッチS713002

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	C₇H₅N₅S₂
	分子量	223.28	CAS No.	2645-32-1
Solubility (25°C)*	体外	DMSO	45 mg/mL (201.54 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	PR-619 is a non-selective, reversible inhibitor of the deubiquitinylating enzymes (DUBs) with EC50 of 1-20 μM in a cell-free assay. PR-619 activates autophagy.
in vitro	PR-619 is a cell-permeable pyridinamine class broad-spectrum DUB inhibitor whose known targets include ATXN3, BAP1, JOSD2, OTUD5, UCH-L1, UCH-L3, UCH-L5/UCH37, USP1, 2, 4, 5, 7, 8, 9X, 10, 14, 15, 16, 19, 20, 22, 24, 28, 47, 48, VCIP135, YOD1, as well as deISGylase PLpro, deNEDDylase DEN1, and deSUMOlyase SENP6. PR-619 are shown to increase overall protein polyubiquitination in HEK293T cells in a dose- and time-dependent manner (20 to 150 μM, 0.5 to 20 h). PR619 treatment results in upregulation of both K ⁴⁸ - and K⁶³-linked polyUb chains. PR-619 induces HCT116 cell death with EC50 values of 6.3 μM.^[1]
in vivo	PR-619 enhances the antitumor effect of cisplatin on a cisplatin-naive and cisplatin-resistant UC xenograft of nude mice.

プロトコル(参考用のみ)

キナーゼアッセイ	Ub-PLA₂ assay
キナーゼアッセイ	Recombinant enzymes in 20 mM Tris-HCl, pH 8.0, 2 mM CaCl₂ and 2 mM β-mercaptoethanol (DUB assay buffer) are preincubated with single doses or dose ranges of PR-619 or P22077 for 30 minutes in a 96 well plate before the addition of Ub-PLA₂ and NBD C6-HPC. The liberation of a fluorescent product within the linear range of the assay is monitored at room temperature using a fluorescence plate reader. Vehicle (2%(v/v) DMSO) and 10 mM N-ethylmaleimide are included as controls. Where ≥60% inhibition is observed, EC50 values are determined using a sigmoidal dose response equation.
細胞アッセイ	細胞株	HCT116, HEK293T
	濃度	0.5-50 μM
	反応時間	72 h
	実験の流れ	72 h hours later, 0.2 mg/mL resazurin prepared in phosphate-buffered saline is added to each well and the cells are incubated for an additional 3-6 h. The fluorescence of the resazurin reduction product is measured using Ex=535 nm and Em=590 nm filters on a fluorimeter. The EC50 values are calculated in Prism.
動物実験	動物モデル	Nude mice
	投薬量	10 mg/kg
	投与方法	i.p.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Front Pharmacol, 2017, https://doi.org/10.3389/fphar.2017.00565]

: Data from [Data independently produced by , , Front Pharmacol, 2018, 8:565]

: Data from [Data independently produced by , , Anim Reprod Sci, 2017, 187:64-73]

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：

Noncanonical function of folate through folate receptor 1 during neural tube formation [ Nat Commun, 2024, 15(1):1642]	PubMed: 38388461
Precise pancreatic cancer therapy through targeted degradation of mutant p53 protein by cerium oxide nanoparticles [ J Nanobiotechnology, 2023, 21(1):117]	PubMed: 37005668
Comparative proteomic and phosphoproteomic analysis reveals differential heat response mechanism in two congeneric oyster species [ Ecotoxicol Environ Saf, 2023, 263:115197]	PubMed: 37451098
Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models [ Biomedicines, 2023, 10.3390/biomedicines11030759]	PubMed: 36979739
A Novel Recognition by the E3 Ubiquitin Ligase of HSV-1 ICP0 Enhances the Degradation of PML Isoform I to Prevent ND10 Reformation in Late Infection [ Viruses, 2023, 15(5)1070]	PubMed: 37243155
Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer-In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models [ Biomedicines, 2023, 11(3)759]	PubMed: 36979739
An indispensable role of TAZ in anoikis resistance promoted by OTUB1 deubiquitinating enzyme in basal-like triple-negative breast cancer cells [ Biochem Biophys Res Commun, 2023, 649:1-9]	PubMed: 36738577
Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis [ Cell Res, 2022, 1-17]	PubMed: 35821088
Substitution of PINK1 Gly411 modulates substrate receptivity and turnover [ Autophagy, 2022, 1-22.]	PubMed: 36469690
Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation [ Cell Death Differ, 2022, 10.1038/s41418-022-00983-4]	PubMed: 35379950

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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