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Purity: ≥98%
PR-619 (PR619; PR 619) is a novel, cell-permeable, non-selective and reversible inhibitor of the deubiquitinylating enzymes (DUBs) with potential antineoplastic activity. It inhibits DUB with an EC50 of 1-20 μM in a cell-free assay. PR-619 has a broad-range activity against DUBs and potently suppresses the activity of almost all cysteine protease DUBs, but shows high selectivity toward DUBs over other proteases, such as calpain 1, or cathepsins. PR-619 induces (tumor) cell death with EC50 values in the low micromolar range.
Targets |
USP4(EC50= 3.93 μM);USP8(EC50= 4.9 μM);USP7(EC50= 6.86 μM);USP2(EC50= 7.2 μM);USP5(EC50= 8.61 μM)
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ln 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.
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ln Vivo |
Cisplatin's antitumor effect is enhanced by PR-619 (10 mg/kg/day) in a Cisplatin-Na ve and Cisplatin-resistant UC Xenograft of nude mice[2].
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Enzyme Assay |
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.
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Cell Assay |
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.
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Animal Protocol |
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References |
Molecular Formula |
C7H5N5S2
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Molecular Weight |
223.28
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Exact Mass |
223.00
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Elemental Analysis |
C, 37.66; H, 2.26; N, 31.37; S, 28.72
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CAS # |
2645-32-1
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Appearance |
Dark mustard yellow fluffy powder
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SMILES |
S(C#N)C1C(N([H])[H])=NC(=C(C=1[H])SC#N)N([H])[H]
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InChi Key |
ZXOBLNBVNROVLC-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C7H5N5S2/c8-2-13-4-1-5(14-3-9)7(11)12-6(4)10/h1H,(H4,10,11,12)
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Chemical Name |
(2,6-diamino-5-thiocyanatopyridin-3-yl) thiocyanate
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Synonyms |
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : 3~21 mg/mL ( 13.43~94.05 mM)
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 4.4787 mL | 22.3934 mL | 44.7868 mL | |
5 mM | 0.8957 mL | 4.4787 mL | 8.9574 mL | |
10 mM | 0.4479 mL | 2.2393 mL | 4.4787 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
[1] Chem Biol.2011 Nov 23;18(11):1401-12. td> |
[1] Chem Biol.2011 Nov 23;18(11):1401-12. td> |
Figure 1. PR-619 induced cytotoxicity and apoptosis in human urothelial carcinoma cells in a dose-dependent and time-dependent manner. Cells. [4].2019 Oct 17;8(10):1268. td> |
Figure 2. PR-619 induced ER stress and ER-stress-related apoptosis in human urothelial carcinoma (UC) cells.[4].2019 Oct 17;8(10):1268. td> |