Conditionnement : 25mg
Téléphone : +1 850 650 7790
Synonyms: PR 619, 2,6-Diamino-3,5-dithiocyanopyridine
| Description | PR-619 (2,6-Diamino-3,5-dithiocyanopyridine) is a DUB inhibitor that inhibits USP2/4/5/7/8 (EC50=7.2/3.93/8.61/6.86/4.9 μM). PR-619 induces endoplasmic reticulum stress and activates autophagy. |
| Targets & IC50 | USP8:4.90 μM(EC50), SENP6 core:2.37 μM(EC50), USP4:3.93 μM(EC50), UCHL3:2.95 μM(EC50), JOSD2:1.17 μM(EC50) |
| In vitro | METHODS: HEK293T cells were treated with PR-619 (5-50 µM) for 6 h. Target protein expression levels were measured by Western Blot. RESULTS: PR-619 interfered with probe labeling at concentrations of 5 µM and above. PR-619 inhibited probe labeling of USP7, but also targeted many other DUBs in the same concentration range, consistent with its broader inhibitory profile. [1] METHODS: The leukemia cell line K562 was treated with PR-619 (40 µM) for 2 h. Targeting was detected by Immunofluorescence. RESULTS: PR-619 induced a different distribution of TOP2A and TOP2B fluorescence signals, consisting of large signal foci. FK2 ubiquitin fluorescence signals partially overlapped with those of TOP2A and TOP2B, as well as SUMO2/3. [2] |
| In vivo | METHODS: To detect anti-tumor activity in vivo, PR-619 (10 mg/kg once daily) and cisplatin (10 mg/kg three times weekly) were intraperitoneally injected into Nude mice bearing T24 or BFTC-905 xenografts for three weeks. RESULTS: The combination of cisplatin and PR-619 showed the most significant antitumor effects on T24 and BFTC-905 xenograft tumors compared to monotherapy. [3] |
| Synonyms | PR 619, 2,6-Diamino-3,5-dithiocyanopyridine |
| Kinase Assay | Ub-PLA2 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. |
| Cell Research | 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.(Only for Reference) |
| Molecular Weight | 223.28 |
| Formula | C7H5N5S2 |
| Cas No. | 2645-32-1 |
| Smiles | Nc1nc(N)c(SC#N)cc1SC#N |
| Relative Density. | 1.61 g/cm3 (Predicted) |
| Storage | Store at low temperature Powder: -20°C for 3 years | In solvent: -80°C for 1 year Shipping with blue ice/Shipping at ambient temperature. | |||||||||||||||||||||||||||||||||||
| Solubility Information | DMSO: 55 mg/mL (246.33 mM), Sonication is recommended.  | |||||||||||||||||||||||||||||||||||
Solution Preparation Table | ||||||||||||||||||||||||||||||||||||
DMSO
Note : The dilution table applies only to solid products. For liquid products, please calculate the stock solution based on the stated concentration and/or density. | ||||||||||||||||||||||||||||||||||||
For example, if the intended dosage is 10 mg/kg for animals weighing 20 g , with a dosing volume of 100 μL per animal, and a total of 10 animals are to be administered, using a formulation of 
10% DMSO+ 40% PEG300+ 5% Tween 80+ 45% Saline/PBS/ddH2O , the resulting working solution concentration would be 2 mg/mL.Dissolve 2 mg of the compound in 100 μL DMSO to obtain a stock solution at a concentration of 20 mg/mL . If the required concentration exceeds the compound's known solubility, please contact us for technical support before proceeding.
1) Add 100 μL of the DMSO stock solution to 400 µL PEG300 and mix thoroughly until the solution becomes clear.
2) Add 50 µL Tween 80 and mix well until fully clarified.
3) Add 450 µL Saline,PBS or ddH2O and mix thoroughly until a homogeneous solution is obtained.
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