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Deubiquitylating enzymes (DBUs) inhibitor
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10mM (in 1mL DMSO)
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Evaluation Sample
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(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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
Cas No.2645-32-1
Solubility≥11.15mg/mL in DMSO
Chemical Name(2,6-diamino-5-thiocyanatopyridin-3-yl) thiocyanate
SDFDownload SDF
Canonical SMILESC1=C(C(=NC(=C1SC#N)N)N)SC#N
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor 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.


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.

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)  

Quality Control

Chemical structure


Related Biological Data


Related Biological Data