MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 531266 | Name: PR-619
Featured New

Description:

WARNING: This product is for research use only, not for human or veterinary use.

PR-619 is a non-selective, reversible inhibitor of the deubiquitinylating enzymes (DUBs) with EC50 of 1-20 μM in a cell-free assay. PR-619 induces cytotoxicity, apoptosis, and cell cycle arrest at the G0/G1 stage by activating caspases, PARP cleavage, and p21.

Chemical Structure

PR-619
PR-619
CAS#2645-32-1

Theoretical Analysis

MedKoo Cat#: 531266

Name: PR-619

CAS#: 2645-32-1

Chemical Formula: C7H5N5S2

Exact Mass: 222.9986

Molecular Weight: 223.27

Elemental Analysis: C, 37.66; H, 2.26; N, 31.37; S, 28.72

Price and Availability

Size Price Availability Quantity
25mg USD 90.00 Ready to ship
50mg USD 150.00 Ready to ship
100mg USD 225.00 Ready to ship
200mg USD 350.00 Ready to ship
500mg USD 550.00 Ready to ship
1g USD 950.00 Ready to ship
2g USD 1,650.00 Ready to ship
5g USD 3,650.00 Ready to ship
Show More
Bulk Inquiry
Buy Now
Add to Cart
Related CAS #
No Data
Synonym
PR-619; PR 619; PR619.
IUPAC/Chemical Name
(2,6-diamino-5-thiocyanatopyridin-3-yl) thiocyanate
InChi Key
ZXOBLNBVNROVLC-UHFFFAOYSA-N
InChi Code
InChI=1S/C7H5N5S2/c8-2-13-4-1-5(14-3-9)7(11)12-6(4)10/h1H,(H4,10,11,12)
SMILES Code
N#CSC1=C(N)N=C(N)C(SC#N)=C1
Appearance
Dark mustard yellow fluffy powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
PR-619 is a broad-range and reversible DUB inhibitor with EC50s of 3.93, 4.9, 6.86, 7.2, and 8.61 μM for USP4, USP8, USP7, USP2, and USP5, respectively.
In vitro activity:
To assess the cytotoxic potential of PR-619, OLN-t40 cells were incubated for 24 h with various concentrations. Cell viability was determined by MTT assay and revealed that PR-619 exerted concentration-dependent cytotoxicity in a very narrow concentration range of 7–10 μM. Half maximal cytotoxicity was observed after a 24 h treatment with 9–10 μM, which also caused the cells to retract their processes and appear morphologically damaged (Fig. 1A, B). Fig. 1C demonstrates that PR-619 (up to 40 μM) added directly to a cell lysate for 30 min did not exert a significant inhibitory effect on proteasomal activity, while MG-132 (10 μM) completely abolished proteasomal activity in cell lysates within 30 min. In contrast thereto, when live cells were incubated with PR-619 (9 μM, 24 h) proteasomal activity was reduced to 50% (Fig. 1C). After treatment with MG-132 (3 μM, 24 h) proteasomal activity was impaired and remained at a 40% level. Hence, 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. Reference: Biochim Biophys Acta. 2012 Nov;1823(11):2057-68. https://linkinghub.elsevier.com/retrieve/pii/S0167-4889(12)00102-4
In vivo activity:
Either the vehicle (dimethyl sulfoxide) or PR-619 (100 μg) was intraperitoneally administered to mice after UUO induction once a day for 7 days. Administration of PR-619 attenuated renal fibrosis with downregulation of mesenchymal markers, extracellular matrix proteins, matrix metalloproteinases, apoptosis, macrophage infiltration, and the TGF-β1 mRNA level in UUO mice. Although type I TGF-β receptor (TGF-βRI), Smad2, Smad3, and Smad4 protein expression levels were markedly increased in mice with UUO, administration of PR-619 suppressed only Smad4 expression but not TGF-βRI, Smad2, or Smad3 expression. PR-619 also had an inhibitory effect on TGF-β1-induced α-smooth muscle actin expression and reduced Smad4 levels in NRK-49F cells. These results indicate that PR-619 ameliorates renal fibrosis, which is accompanied by the reduction of Smad4 expression. Reference: PLoS One. 2018 Aug 16;13(8):e0202409. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/30114247/
Solvent mg/mL mM comments
Solubility
DMSO 20.0 89.60
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 223.27 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
1. Hu X, Zhuang D, Zhang R, Sun X, Lu Q, Dai Y. The small molecule inhibitor PR-619 protects retinal ganglion cells against glutamate excitotoxicity. Neuroreport. 2020 Nov 4;31(16):1134-1141. doi: 10.1097/WNR.0000000000001522. PMID: 32991521. 2. Wang L, Li M, Sha B, Hu X, Sun Y, Zhu M, Xu Y, Li P, Wang Y, Guo Y, Li J, Shi J, Li P, Hu T, Chen P. Inhibition of deubiquitination by PR-619 induces apoptosis and autophagy via ubi-protein aggregation-activated ER stress in oesophageal squamous cell carcinoma. Cell Prolif. 2021 Jan;54(1):e12919. doi: 10.1111/cpr.12919. Epub 2020 Oct 31. PMID: 33129231; PMCID: PMC7791184.
In vivo protocol:
1. Soji K, Doi S, Nakashima A, Sasaki K, Doi T, Masaki T. Deubiquitinase inhibitor PR-619 reduces Smad4 expression and suppresses renal fibrosis in mice with unilateral ureteral obstruction. PLoS One. 2018 Aug 16;13(8):e0202409. doi: 10.1371/journal.pone.0202409. PMID: 30114247; PMCID: PMC6095583.
1: Li WT, Jin X, Song SJ, Wang C, Fu C, Jiang W, Bai J, Shi ZZ. Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells. Anim Cells Syst (Seoul). 2024 May 11;28(1):237-250. doi: 10.1080/19768354.2024.2346981. PMID: 38741950; PMCID: PMC11089935. 2: Lin WC, Chiu YL, Kuo KL, Chow PM, Hsu CH, Liao SM, Dong JR, Chang SC, Liu SH, Liu TJ, Hsu FS, Wang KC, Lin YC, Chang CC, Huang KY. Anti-tumor effects of deubiquitinating enzyme inhibitor PR-619 in human chondrosarcoma through reduced cell proliferation and endoplasmic reticulum stress-related apoptosis. Am J Cancer Res. 2023 Jul 15;13(7):3055-3066. PMID: 37559983; PMCID: PMC10408468. 3: Wu J, Liu C, Wang T, Liu H, Wei B. Deubiquitinase inhibitor PR-619 potentiates colon cancer immunotherapy by inducing ferroptosis. Immunology. 2023 Nov;170(3):439-451. doi: 10.1111/imm.13683. Epub 2023 Aug 1. PMID: 37526037. 4: Nowak Ł, Krajewski W, Dejnaka E, Małkiewicz B, Szydełko T, Pawlak A. Ubiquitin-Specific Proteases as Potential Therapeutic Targets in Bladder Cancer- In Vitro Evaluation of Degrasyn and PR-619 Activity Using Human and Canine Models. Biomedicines. 2023 Mar 2;11(3):759. doi: 10.3390/biomedicines11030759. PMID: 36979739; PMCID: PMC10045593. 5: Fu J, Yu M, Xu W, Yu S. High Expression of G9a Induces Cisplatin Resistance in Hepatocellular Carcinoma. Cell J. 2023 Feb 1;25(2):118-125. doi: 10.22074/cellj.2022.557564.1077. PMID: 36840458; PMCID: PMC9968374. 6: Tao Y, You W. The Deubiquitinating Enzyme USP4 Functions as an Oncoprotein in Gastric Cancer and Mediates NF-κB Signaling by Regulating PRL-3 Expression. Front Biosci (Landmark Ed). 2022 Oct 19;27(10):286. doi: 10.31083/j.fbl2710286. PMID: 36336860. 7: Große M, Setz C, Rauch P, Auth J, Morokutti-Kurz M, Temchura V, Schubert U. Inhibitors of Deubiquitinating Enzymes Interfere with the SARS-CoV-2 Papain-like Protease and Block Virus Replication In Vitro. Viruses. 2022 Jun 27;14(7):1404. doi: 10.3390/v14071404. PMID: 35891385; PMCID: PMC9324251. 8: Hsu FS, Lin WC, Kuo KL, Chiu YL, Hsu CH, Liao SM, Dong JR, Liu SH, Chang SC, Yang SP, Chen YT, Chang RJ, Huang KH. PR-619, a General Inhibitor of Deubiquitylating Enzymes, Diminishes Cisplatin Resistance in Urothelial Carcinoma Cells through the Suppression of c-Myc: An In Vitro and In Vivo Study. Int J Mol Sci. 2021 Oct 28;22(21):11706. doi: 10.3390/ijms222111706. PMID: 34769137; PMCID: PMC8584183. 9: Sen E, Kota KP, Panchal RG, Bavari S, Kiris E. Screening of a Focused Ubiquitin-Proteasome Pathway Inhibitor Library Identifies Small Molecules as Novel Modulators of Botulinum Neurotoxin Type A Toxicity. Front Pharmacol. 2021 Sep 27;12:763950. doi: 10.3389/fphar.2021.763950. PMID: 34646144; PMCID: PMC8503599. 10: Talreja J, Bauerfeld C, Wang X, Hafner M, Liu Y, Samavati L. MKP-1 modulates ubiquitination/phosphorylation of TLR signaling. Life Sci Alliance. 2021 Sep 27;4(12):e202101137. doi: 10.26508/lsa.202101137. PMID: 34580177; PMCID: PMC8500224. 11: Cho CC, Li SG, Lalonde TJ, Yang KS, Yu G, Qiao Y, Xu S, Ray Liu W. Drug Repurposing for the SARS-CoV-2 Papain-Like Protease. ChemMedChem. 2022 Jan 5;17(1):e202100455. doi: 10.1002/cmdc.202100455. Epub 2021 Oct 12. Erratum in: ChemMedChem. 2022 Mar 4;17(5):e202200053. doi: 10.1002/cmdc.202200053. PMID: 34423563; PMCID: PMC8653067. 12: Cai B, Hou M, Zhang S, Xin Z, Huang J, Yang J, Wang Y, Cai X, Xie S, Zhang C, Huang Y. Dual Targeting of Endoplasmic Reticulum by Redox-Deubiquitination Regulation for Cancer Therapy. Int J Nanomedicine. 2021 Jul 30;16:5193-5209. doi: 10.2147/IJN.S321612. PMID: 34354353; PMCID: PMC8331122. 13: Barban do Patrocínio A, Cabral FJ, de Paiva TH, Magalhães LG, Paula LAL, Brigato OM, Guerra-Sá R, Rodrigues V. Deubiquitinating enzymes as possible drug targets for schistosomiasis. Acta Trop. 2021 May;217:105856. doi: 10.1016/j.actatropica.2021.105856. Epub 2021 Feb 9. PMID: 33577811. 14: Wang L, Li M, Sha B, Hu X, Sun Y, Zhu M, Xu Y, Li P, Wang Y, Guo Y, Li J, Shi J, Li P, Hu T, Chen P. Inhibition of deubiquitination by PR-619 induces apoptosis and autophagy via ubi-protein aggregation-activated ER stress in oesophageal squamous cell carcinoma. Cell Prolif. 2021 Jan;54(1):e12919. doi: 10.1111/cpr.12919. Epub 2020 Oct 31. PMID: 33129231; PMCID: PMC7791184. 15: Hu X, Zhuang D, Zhang R, Sun X, Lu Q, Dai Y. The small molecule inhibitor PR-619 protects retinal ganglion cells against glutamate excitotoxicity. Neuroreport. 2020 Nov 4;31(16):1134-1141. doi: 10.1097/WNR.0000000000001522. PMID: 32991521. 16: Safa N, Pettigrew JH, Gauthier TJ, Melvin AT. Direct measurement of deubiquitinating enzyme activity in intact cells using a protease-resistant, cell-permeable, peptide-based reporter. Biochem Eng J. 2019 Nov 15;151:107320. doi: 10.1016/j.bej.2019.107320. Epub 2019 Jul 29. PMID: 32831622; PMCID: PMC7442178. 17: Kitagawa T, Takiya S. Regulation of genes for ubiquitination and SUMO- specific protease involved in larval development of the silkworm, Bombyx mori. Dev Growth Differ. 2020 Aug;62(6):438-449. doi: 10.1111/dgd.12687. PMID: 32573769. 18: Mirzapoiazova T, Pozhitkov A, Nam A, Mambetsariev I, Nelson MS, Tan YC, Zhang K, Raz D, Singhal S, Nasser MW, Kulkarni P, Batra SK, Sattler M, Salgia R. Effects of selected deubiquitinating enzyme inhibitors on the proliferation and motility of lung cancer and mesothelioma cell lines. Int J Oncol. 2020 Jul;57(1):80-86. doi: 10.3892/ijo.2020.5034. Epub 2020 Apr 1. PMID: 32236606; PMCID: PMC7252467. 19: He D, Li M, Damaris RN, Bu C, Xue J, Yang P. Quantitative ubiquitylomics approach for characterizing the dynamic change and extensive modulation of ubiquitylation in rice seed germination. Plant J. 2020 Mar;101(6):1430-1447. doi: 10.1111/tpj.14593. Epub 2019 Dec 11. PMID: 31677306. 20: Kuo KL, Liu SH, Lin WC, Chow PM, Chang YW, Yang SP, Shi CS, Hsu CH, Liao SM, Chang HC, Huang KH. The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study. Cells. 2019 Oct 17;8(10):1268. doi: 10.3390/cells8101268. PMID: 31627336; PMCID: PMC6830310.