PR-619
PR-619 (CAS: 2645-32-1) is a cell-permeable, reversible small molecule inhibitor targeting cysteine-dependent deubiquitinating enzymes (DUBs). By broadly suppressing the enzymatic activity of these DUBs, PR-619 promotes the accumulation of ubiquitinated proteins within cells. Unlike proteasome inhibitors such as MG-132, PR-619 does not directly inhibit proteasomal catalytic activity in cell lysates, exerting its inhibitory effects selectively in intact cells. Experimental findings indicate that PR-619 causes cytotoxicity at low micromolar concentrations and stabilizes microtubule networks, inducing tau aggregation—features relevant to cancer biology and neurodegeneration research.
- 1. Anat Raiff, Shidong Zhao, et al. "TOM20 - driven E3 ligase recruitment regulates mitochondrial dynamics through PLD6." Nat Chem Biol. 2025 Apr 22 PMID: 40263465
- 2. Lei Pang, Yuanzhi Huang, et al. "The adaptor protein AP-3β disassembles heat-induced stress granules via 19S regulatory particle in." Nat Commun. 2025 Feb 27;16(1):2039. PMID: 40016204
- 3. Hongbin Yang, Shahd Fouad, et al. "Cyclin F–EXO1 axis controls cell cycle–dependent execution of double-strand break repair." Sci Adv. 2024 Aug 9;10(32):eado0636. PMID: 39121215
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 223.28 |
| Cas No. | 2645-32-1 |
| Formula | C7H5N5S2 |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥11.15 mg/mL in DMSO |
| Chemical Name | (2,6-diamino-5-thiocyanatopyridin-3-yl) thiocyanate |
| SDF | Download SDF |
| Canonical SMILES | Nc(c(SC#N)c1)nc(N)c1SC#N |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
OLN-t40 cells; GFP-LC3-OLN cells |
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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. |
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Reaction Conditions |
Indirect immunofluorescence assay: 18 h. |
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Applications |
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. |
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References: [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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| 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 & MSDS
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Chemical structure
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Related Biological Data
