[CAS NO. 2645-32-1] PR-619
PRODUCTS SPECIFICATIONS [2645-32-1]
DESCRIPTION [2645-32-1]
Overview
| MDL | MFCD00830384 |
|---|---|
| Molecular Weight | 223.28 |
| Molecular Formula | C7H5N5S2 |
| SMILES | NC1=C(SC#N)C=C(SC#N)C(N)=N1 |
9 Publications Citing Use of MCE
- [1]Nat Commun. 2022 Mar 31;13(1):1700.
- [2]J Clin Invest. 2022 Jul 14;e156501.
- [3]Cell Death Differ. 2022 Sep 14.
- [4]J Med Chem. 2022 Oct 11.
- [5]Cell Prolif. 2021 Jan;54(1):e12919.
- [6]FASEB J. 2021 Aug;35(8):e21800.
- [7]Ann Transl Med. 2023 Jan 31; 11(2):73.
- [8]Front Biosci (Landmark Ed). 2022, 27(10), 286.
- [9]Patent. US20180263995A1.
Summary
IC50 & Target
EC50: 3.93 μM (USP4), 4.9 μM (USP8), 6.86 μM (USP7), 7.2 μM (USP2), 8.61 μM (USP5) [1]
In Vitro
PR-619, a deubiquitylase inhibitor, prevents degradation, indicating KCa3.1 is targeted for degradation by ubiquitylation
[2]
.
PR-619 affects the microtubule network and led to the accumulation of small punctuated tau deposits around. PR-619 causes the dephosphorylation of tau
[3]
.
PR-619 (7-12.5 μM) causes an increase in the abundance of ubiquitinated proteins within 24 h. PR-619 leads to the induction of heat shock proteins and to an increase of ubiquitinated proteins
[3]
.
PR-619 (9 μM) affects the organization of the microtubule network in OLN-t40 cells
[3]
.
PR-619 (5, 7.5, and 10 μM) induces ER Stress and ER-Stress related apoptosis on T24 and BFTC-905 cells. PR-619 induces polyubiquitination, Bcl-2 downregulation, and concurrent PARP cleavage in a dose-dependent manner. PR-619 induces G0/G1 arrest in UC cells
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cytotoxicity Assay [1]
| Cell Line: | OLN-t40 cells. |
| Concentration: | 0-10 μM. |
| Incubation Time: | 24 hours. |
| Result: | Exerted concentration-dependent cytotoxicity in a very narrow concentration range of 7-10 μM. |
In Vivo
PR-619 (10 mg/kg/day) enhances the antitumor effect of Cisplatin on a Cisplatin-Naïve and Cisplatin-resistant UC Xenograft of nude mice
[4]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Nude mice [4] . |
| Dosage: | 10 mg/kg/day (Cisplatin combined). |
| Administration: | Intraperitoneally. |
| Result: | Enhanced the antitumor effect of Cisplatin. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 21 mg/mL ( 94.05 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 4.4787 mL | 22.3934 mL | 44.7868 mL |
| 5 mM | 0.8957 mL | 4.4787 mL | 8.9574 mL |
| 10 mM | 0.4479 mL | 2.2393 mL | 4.4787 mL |
-
1.
References
- [1] Altun M, et al. Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes. Chem Biol. 2011 Nov 23;18(11):1401-12.
- [2] Bertuccio CA, et al. Anterograde trafficking of KCa3.1 in polarized epithelia is Rab1- and Rab8-dependent and recycling endosome-independent. PLoS One. 2014 Mar 14;9(3):e92013.
- [3] Seiberlich V, 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. Biochim Biophys Acta. 2012 Nov;1823(1
- [4] Kuan-Lin Kuo, et al. 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.