foscenvivint (PRI724)

Inhibition with ICG-001 significantly attenuated PY-induced fibrosis, confirming Wnt/β-catenin-dependent effects. These findings provide mechanistic insight into PY-induced renal injury and fibrosis.

Furthermore, the senolytic Src inhibitor dasatinib reduced senescence and fibrosis markers and attenuated β-catenin activity, suggesting that Src acts upstream of β-catenin in this context. Inhibition of β-catenin using ICG001 or PRI724 suppressed senescence and fibrosis markers and reduced downstream targets including CTGF and cyclin D1. These findings reveal a mechanistic link between mechanical stiffness, cellular senescence, and fibrosis in uterine fibroids, and identify Src and β-catenin as potential therapeutic targets.

This comprehensive pipeline identified key molecular drivers, upstream regulators, survival-associated biomarkers, and potential therapeutic compounds in gastric cancer. The findings offer a robust framework for future experimental validation and contribute to the development of personalized therapeutic strategies for improving clinical outcomes in gastric cancer.

Targeting β-catenin interactions with co-activators p300/CBP using selective inhibitors (IQ-1 and ICG-001) effectively mitigated Wnt-driven ARSI resistance, restoring sensitivity to therapy in preclinical models...The identified Wnt signature holds potential as a biomarker for predicting and monitoring therapeutic outcomes. Concurrent targeting of AR and Wnt signaling represents a promising strategy to overcome treatment resistance, particularly in patients with Wnt-activating mutations.

Collectively, our study demonstrates that ABCA5 is a potential therapeutic target for PDAC and provides a theoretical basis for a new combination therapy of ABCA5 regulation with gemcitabine and WNT inhibitor.

This study evaluated PRI-724, a CBP/β-catenin inhibitor, in patient-derived drug-naïve melanoma cells and their trametinib- or vemurafenib-resistant counterparts. The results of the study point to the potential of PRI-724 as a chemotherapeutic agent for the treatment of melanoma. Its efficacy might depend on CBP/β-catenin transcriptional activity in melanoma cells, and further evaluation of this signaling with survivin as a biomarker is therefore warranted.

To further dissect its mechanism, Wnt signalling was perturbed using siRNA against GSK3β, β-catenin and ICG-001 (a CBP/β-catenin interaction inhibitor), and their combination...This study identifies miR-195-5p as a potent regulator of CSCs and proliferation, and modulator of the Wnt signalling cascade. Co-inhibition of GSK3β and CBP/β-catenin through miR-195-5p highlights its therapeutic potential in combating stemness and proliferation in breast cancer.

This study demonstrates the functionality of SH3RF2 in both potentiating tumor progression and inducing M2 macrophage polarization through coordinated regulation of LZTS2 degradation and β-catenin nuclear translocation. These findings establish a novel mechanistic framework and propose SH3RF2-associated signaling axes as promising therapeutic targets for LUSC.

Pharmacological suppression of the β-Catenin pathway using ICG-001 established NF-κB as its downstream signaling mediator...FPN1 deficiency-induced iron overload exacerbates ROS production, triggering neuroinflammation, which may potentiate microglial activation and the IL-6/STAT3 pathway. The subsequent hepcidin-mediated iron sequestration reduces iron availability in the PFC and hippocampus, ultimately disrupting synaptogenesis and neuronal excitability, and culminating in depression-like behaviors.

Our study revealed that β-catenin activation drives sorafenib resistance in HCC, and disrupting β-catenin enhances sorafenib efficacy by promoting apoptosis and inhibiting proliferation. The combination of sorafenib and PRI-724, a Wnt/β-catenin inhibitor, showed synergistic anti-tumor effects in vitro across various HCC cell lines, in vivo using xenograft models, ex vivo utilizing MDT chip system to explore clinical applications, offering a novel therapeutic strategy for HCC patients.

Regardless of drug tolerance differences, both VemR models display resistance to MEK inhibitor and sensitivity to Wnt/β-catenin inhibitor, ICG-001. These data implicate an important role for Wnt/β-catenin signaling in VemR-induced metabolic plasticity. Our data demonstrate that drug tolerance thresholds play a direct role in driving metabolic shifts towards specific routes, thus providing a new basis for delineating VemR melanomas for metabolism-targeting therapies.

MITF and β-catenin levels were induced and treatment with Wnt/β-catenin inhibitor ICG-001 restored vemurafenib sensitivity with concomitant reductions in β-catenin-regulated gene expressions, phospho-ERK1/2, and VemR-induced mitochondrial mass and respiration. Pathways associated with cytokine-cytokine receptor, ECM receptor, and neuroactive ligand receptor interactions were similarly enriched in BRAFV600E patient-derived melanoma as M14 and A2058 cells whereas distinct pathways involving cell cycle, DNA replication, Fanconi anemia and DNA repair pathways are upregulated in wild type BRAF expressing patient derived melanoma. These data show for the first time that the metabolic pathway choices made by VemR BRAF mutant melanomas are controlled by vemurafenib tolerance and endurance thresholds and Wnt/β-catenin signaling plays a central role in coordinating expression of genes controlling VemR and metabolic pathway shifts.