PR-619

SKU: orb1307302

Description

PR-619 is a broad-spectrum deubiquitinase (DUB) inhibitor targeting USP2, USP4, USP5, USP7, and USP8. This cell-permeable compound is widely used in research to study proteasomal degradation, endoplasmic reticulum stress, and autophagy pathways in both cellular and animal models.

Research Area

Protein Biochemistry

Key Properties

• CAS Number: 2645-32-1
• MW: 223.28
• Purity: >98%
• Formula: C₇H₅N₅S₂
• SMILES: Nc1nc(N)c(SC#N)cc1SC#N
• Target: DUB (Deubiquitinating enzyme)
• Solubility: Soluble in DMSO (up to 5 mg/ml).

Bioactivity

• Target IC50:
  USP4:3.93 μM(EC50)|UCHL3:2.95 μM(EC50)|JOSD2:1.17 μM(EC50)|USP8:4.90 μM(EC50)|SENP6 core:2.37 μM(EC50)
• In Vivo:
  METHODS: To detect anti-tumor activity in vivo, PR-619 (10 mg/kg once daily) and cisplatin (10 mg/kg three times weekly) were intraperitoneally injected into Nude mice bearing T24 or BFTC-905 xenografts for three weeks. RESULTS: The combination of cisplatin and PR-619 showed the most significant antitumor effects on T24 and BFTC-905 xenograft tumors compared to monotherapy.
• In Vitro:
  METHODS: HEK293T cells were treated with PR-619 (5-50 µM) for 6 h. Target protein expression levels were measured by Western Blot. RESULTS: PR-619 interfered with probe labeling at concentrations of 5 µM and above. PR-619 inhibited probe labeling of USP7, but also targeted many other DUBs in the same concentration range, consistent with its broader inhibitory profile. METHODS: The leukemia cell line K562 was treated with PR-619 (40 µM) for 2 h. Targeting was detected by Immunofluorescence. RESULTS: PR-619 induced a different distribution of TOP2A and TOP2B fluorescence signals, consisting of large signal foci. FK2 ubiquitin fluorescence signals partially overlapped with those of TOP2A and TOP2B, as well as SUMO2/3.
• Cell Research:
  72 h hours later, 0.2 mg/mL resazurin prepared in phosphate-buffered saline is added to each well and the cells are incubated for an additional 3-6 h. The fluorescence of the resazurin reduction product is measured using Ex=535 nm and Em=590 nm filters on a fluorimeter. The EC50 values are calculated in Prism.(Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

3,5-Dithiocyanatopyridine-2,6-diamine

Compound Identifiers

PubChem CID

2817763