PR-619

产品说明书

Print
Chemical Structure| 2645-32-1 同义名 : 2,6-Diamino-3,5-dithiocyanopyridine; DUB Inhibitor V
CAS号 : 2645-32-1
货号 : A244244
分子式 : C7H5N5S2
纯度 : 99%+
分子量 : 223.28
MDL号 : MFCD00830384
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 20 mg/mL(89.57 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
生物活性
靶点

  • DUB

    Plpro, EC50:14.2 μM

  • UCH

    UCH-L5, EC50:12.8 μM

    UCH-L3, EC50:2.95 μM

  • USP/UBP

    USP28, EC50:6.24 μM

    USP5, EC50:4.90 μM
描述 Deubiquitinating enzymes (DUBs) remove ubiquitin from their substrates and, together with ubiquitin ligases, play an important role in the regulation of protein expression. PR-619 is a broad-range UDB inhibitor that led to cell morphological changes, the upregulation of HSPs and accumulation of ubiquitinated protein species. PR-619 exhibits concentration dependent cytotoxicity in very narrow concentration range of 7 - 10 μM to OLN 93 cells. Treatment with 9 μM PR-619 causes an increase in the abundance of ubiquitinated protein, and proteasomal activity reduce to 50% within 24 h. PR-619 promotes the association of tau, ubiquitin and p62 with microtubules and alter their solubility[3]. In addition, Treatment with the PR-619 increased caspase-8 ubiquitination and caspase-8 enzymatic activity and sensitized normal fibroblasts to TRAIL-mediated apoptosis[4]. In vivo, administered daily with 100 μg PR-619 improves renal histopathological changes in mice with unilateral ureteral obstruction. Administration of PR-619 also attenuated renal fibrosis with downregulation of mesenchymal markers, extracellular matrix proteins, matrix metalloproteinases, apoptosis, macrophage infiltration, and the TGF-β1 mRNA level[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.48mL

0.90mL

0.45mL

22.39mL

4.48mL

2.24mL

44.79mL

8.96mL

4.48mL
参考文献

[1]Seiberlich V, Goldbaum O, et al. The small molecule inhibitor PR-619 of deubiquitinating enzymes affects the microtubule network and causes protein aggregate formation in neural cells: implications for neurodegenerative diseases. Biochim Biophys Acta. 2012 Nov;1823(11):2057-68.

[2]Altun M, Kramer HB, et al. Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem Biol. 2011 Nov 23;18(11):1401-12.

[3]Seiberlich V, Goldbaum O, Zhukareva V, Richter-Landsberg C. The small molecule inhibitor PR-619 of deubiquitinating enzymes affects the microtubule network and causes protein aggregate formation in neural cells: implications for neurodegenerative diseases. Biochim Biophys Acta. 2012 Nov;1823(11):2057-68. doi: 10.1016/j.bbamcr.2012.04.011. Epub 2012 Apr 28. PMID: 22565157.

[4]Crowder RN, Dicker DT, El-Deiry WS. The Deubiquitinase Inhibitor PR-619 Sensitizes Normal Human Fibroblasts to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-mediated Cell Death. J Biol Chem. 2016 Mar 11;291(11):5960-5970. doi: 10.1074/jbc.M115.713545. Epub 2016 Jan 12. PMID: 26757822; PMCID: PMC4786729.

[5]Soji K, Doi S, Nakashima A, Sasaki K, Doi T, Masaki T. Deubiquitinase inhibitor PR-619 reduces Smad4 expression and suppresses renal fibrosis in mice with unilateral ureteral obstruction. PLoS One. 2018 Aug 16;13(8):e0202409. doi: 10.1371/journal.pone.0202409. PMID: 30114247; PMCID: PMC6095583.