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About This Item
Empirical Formula (Hill Notation):
C33H35N6O7P
CAS Number:
Molecular Weight:
658.64
NACRES:
NA.21
SMILES string
O=C(NCC1=CC=CC=C1)N(N(CC2=O)C)[C@]([C@@H](N(C3=O)CC4=CC=CC5=C4N=CC=C5)C)([H])N2[C@H]3CC6=CC=C(C=C6)OP(O)(O)=O
assay
≥98% (HPLC)
form
powder
color
white to beige
solubility
DMSO: 2 mg/mL, clear
storage temp.
-10 to -25°C
Quality Level
General description
PRI-724 (Foscenvivint; OP-724) is a phosphorylated predrug that is hydrolyzed to the ICG-001 analog C-82, a selective inhibitor against β-catenin interaction with CREB-binding protein (CBP; CREBBP), but not p300, resulting in upregulated p300/β-catenin complex. PRI-724 treatment reduces the fibrosis induced by CCl4 (1:4 v/v in mineral oil, 1mL/kg 2x per wk) or bile duct ligation (BDL) in mice in vivo (0.4 mg in PBS/kg i.p. 4x per wk). PRI-724 active metabolite C-829 (10 µM) inhibits β-catenin signaling in isolated primary hepatic stellate cells (HSCs) from mice in cultures. PRI-724 inhibits the transcriptional activity of β-catenin by preventing its interaction with CBP. This inhibition leads to a decrease in the transcription of target genes that are normally activated by the β-catenin/CBP interaction. Studies have demonstrated that PRI-724 not only inhibits cell proliferation in models of hepatocellular carcinoma (HCC) but also induces apoptosis and alters cell cycle dynamics.
Application
PRI-724 has been used:
- to inhibit Wnt signaling pathways and study its anti-tumor activity in hepatocellular carcinoma
- to study its effects in non alcoholic steatohepatitis (NASH)-related liver fibrosis
- to study its role ininhibiting viral replication in the context of SARS-CoV-2
Biochem/physiol Actions
Precursor form of the ICG-001 analog C-82, a selective inhibitor against β-catenin interaction with CREB-binding protein (CBP; CREBBP), but not p300.
Regulatory Information
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Combinations of PRI-724 Wnt/?-Catenin Pathway Inhibitor with Vismodegib, Erlotinib, or HS-173 Synergistically Inhibit Head and Neck Squamous Cancer Cells
Kleszcz R, et al.
International Journal of Molecular Sciences, 24 (2023)
Maximilian A Kelch et al.
Frontiers in microbiology, 14, 1193320-1193320 (2023-06-21)
Expanding antiviral treatment options against SARS-CoV-2 remains crucial as the virus evolves under selection pressure which already led to the emergence of several drug resistant strains. Broad spectrum host-directed antivirals (HDA) are promising therapeutic options, however the robust identification of
Kenzaburo Yamaji et al.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 166, 115379-115379 (2023-08-31)
Nonalcoholic steatohepatitis (NASH) is a progressive fibrotic disease associated with an increased risk of developing hepatocellular carcinoma; at present, no efficient therapeutic strategy has been established. Herein, we examined the efficacy of PRI-724, a potent inhibitor of CBP/β-catenin signaling, for
Hiroyasu Okazaki et al.
Experimental lung research, 45(7), 188-199 (2019-07-13)
Purpose/Aim of the Study: Wnt/β-catenin signaling was reported to be activated in pulmonary fibrosis, and was focused on as a target for antifibrotic therapy. However, the mechanism how the inhibition of Wnt/β-catenin signaling ameliorate pulmonary fibrosis has not been fully
Yosuke Osawa et al.
EBioMedicine, 2(11), 1751-1758 (2016-02-13)
Wnt/β-catenin is involved in every aspect of embryonic development and in the pathogenesis of many human diseases, and is also implicated in organ fibrosis. However, the role of β-catenin-mediated signaling on liver fibrosis remains unclear. To explore this issue, the
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