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PR-619Deubiquitylating enzymes (DBUs) inhibitor


Catalog No. A8212
Size Price Stock Qty
10mM (in 1mL DMSO) $80.00 In stock
Evaluation Sample $28.00 In stock
5mg $40.00 In stock
25mg $100.00 In stock
100mg $280.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure


Related Biological Data


Related Biological Data


Biological Activity

Description PR-619 is a non-selective, reversible inhibitor of the deubiquitinylating enzymes (DUBs) with EC50 of 1-20 μM.
Targets USP2 core USP4 USP20 JOSD2 DEN1  
IC50 7.2 μM (EC50) 3.93 μM (EC50) 5.10 μM (EC50) 1.17 μM (EC50) 4.98 μM (EC50)  


Cell experiment [1]:

Cell lines

OLN-t40 cells; GFP-LC3-OLN cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

Indirect immunofluorescence assay: 18 h.


OLN-t40 cells were stably transfected with plasmids encoding the GFP-LC3 fusion protein, exposed to PR-619 (10 μM) for 18 h, and subjected to indirect immunofluorescence using antibodies against LC3. GFP-LC3-OLN cells were treated with PR-619 (9 μM) for 16 h. After, cells were incubated with LysoTracker Red (250 nM) for 30 min at 37℃. Results indicated that treatment with PR-619 represented a DUB inhibitor with broad specificity. Besides, PR-619 does not impair the autophagic flux.


[1] Veronika Seiberlich, Janika Borchert, VIctora Zhukareva, Christiane Richter-Landsberg. Inhibition of Protein Debiquitination by PR-619 Activates the Autophagic Pathway in OLN-t40 Oligodendroglial Cells. Cell Biochem Biophys , 2013; 67:149–160.

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Chemical Properties

Cas No. 2645-32-1 SDF Download SDF
Chemical Name (2,6-diamino-5-thiocyanatopyridin-3-yl) thiocyanate
Canonical SMILES C1=C(C(=NC(=C1SC#N)N)N)SC#N
Formula C7H5N5S2 M.Wt 223.28
Solubility >11.2mg/mL in DMSO Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

View Related Products By Research Topics


(2,6-diamino-5-thiocyanatopyridin-3-yl) thiocyanate, also designated as PR-619, is a broad-range reversible and cell-permeable inhibitor of deubiquitylating enzyme (DUB)[1][2][3], potently suppresses the activity of almost all cysteine protease DUBs[4], but shows selectivity toward DUBs over other proteases, such as calpain 1, or cathepsins[3]. PR-619 induces (tumor) cell death with EC50 values in the low micromolar range [1].
Deubiquitylating enzyme (DUB), also called ubiquitin isopeptidase or deubiquitinating proteins, performs deubiquitination of target proteins. Ubiquitination, followed by proteasomal degradation, is a process of ubiquitin proteasome system (UPS). Failure of the ubiquitin proteasome system (UPS) and/or the autophagy pathway may result in aggregation of proteins, a pathological hallmark of many neurodegenerative diseases [2].
In OLN-t40 cells, 7-10 μM as the concentration range for PR-619 to exert its cytotoxicity was suggested, half maximal cytotoxicity was observed after a 24h-treatment with 9-10 μM PR-619. Similar to MG-132, PR-619 caused an increase in the abundance of ubiquitinated proteins within 24 h at the concentration range of 7-12.5μM. Tested with OLN-t40 cells, PR-619, unlike MG-132, did not inhibit the enzymatic activity of the proteasome in cellular lysates but only when taken up by living cells[2]. An in vitro system showed that PR-619 was able to stabilize the microtubule network and led to small tau aggregates surrounding the microtubule organizing center [5].
There is still not any available result regarding in vivo treatment in an animal body.
[1]. Mikael Altun, Holger B. Kramer, Lianne I. Willems, et al. Activity-Based Chemical Proteomics Accelerates Inhibitor Development for Deubiquitylating Enzymes. Chemistry & Biology, 2011, 18(11): 1401-1412.
[2]. Veronika Seiberlicha, Olaf Goldbauma, Victoria Zhukareva, 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. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2012, 1823(11): 2057–2068.
[3]. Iraia García-Santisteban, Godefridus J Peters, Elisa Giovannetti, et al. USP1 deubiquitinase: cellular functions, regulatory mechanisms and emerging potential as target in cancer therapy. Molecular Cancer, 2013, 12:91.
[4]. Maria Stella Ritorto, Richard Ewan, Ana B. Perez-Oliva, et al. Screening of DUB activity and specificity by MALDI-TOF mass spectrometry. Nature Communications, 2014, 5:4763.
[5]. Laura J Blair, Bo Zhang and Chad A Dickey, et al. Potential synergy between tau aggregation inhibitors and tau chaperone modulators. Alzheimer's Research & Therapy, 2013, 5:41.