product name PR-619
Description: PR-619, chemical name of (2,6-diamino-5-thiocyanatopyridin-3-yl) thiocyanate, is a non-selective, reversible inhibitor of the deubiquitinylating enzymes (DUBs) with EC50 of 1-20 μM in a cell-free assay. PR-619 is a broad-range reversible and cell-permeable inhibitor of deubiquitylating enzyme (DUB), potently suppresses the activity of almost all cysteine protease DUBs, but shows 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.
References: Chem Biol. 2011 Nov 23;18(11):1401-12.
223.28
Formula
C7H5N5S2
CAS No.
2645-32-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 45 mg/mL (201.5 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19414993/
| In Vitro |
In vitro activity: 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. Kinase 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 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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| In Vivo | |
| Animal model | |
| Formulation & Dosage | |
| References | Chem Biol. 2011 Nov 23;18(11):1401-12. |
