foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma - LARVOL DELTA

Novel Promising Therapeutic Strategies for Advancing the Treatment of KMT2A-Rearranged AML (ASH 2024) - "We selected Asparaginase (ASPN), IACS-010759 (IACS), Disulfiram, Gallein, 5-Azacytidine, Quizartinib, Trametinib, γ-Secretase inhibitor and ICG-001 to be tested either alone or in combination with Venetoclax (VEN) in 3D with ex vivo AML cells and AML patient derived MSCs. We support the use of pediatric AML-PDXs in preclinical testing for their ability to mimic the heterogeneity of drug response, aiding in the identification of tailored second-line treatments. VEN+ASPN combination represents a novel promising therapeutic strategy for advancing the treatment of KMT2A-rearranged AML."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CREBBP • CTNNB1 • FAT1 • FLT3 • KDM5A • KMT2A • NOTCH1 • NRAS • TET2

Cellular and Molecular Effects of Targeting the CBP/β-Catenin Interaction with PRI-724 in Melanoma Cells, Drug-Naïve and Resistant to Inhibitors of BRAFV600 and MEK1/2. (PubMed, Cells) - "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."

Journal • Melanoma • Oncology • Solid Tumor • BIRC5 • CTNNB1

The Transcription Factors NFATc1 and NFATc2 Control Glucocorticoid Resistance in Pediatric T-Cell Acute Lymphoblastic Leukemia (ASH 2023) - "In agreement, NFATc1 or NFATc2 specific gene silencing in 3 T-ALL GC resistant cell line models and primary cells increases dexamethasone response, by restoring GR canonical transcriptional activity through the increase expression of BIM GR target gene (p value <0.05). Overall, we revealed for the first time the involvement of NFATc1 and NFATc2 transcription factors in supporting GC resistance in T-ALL cells by the modulation of cholesterol biosynthesis and Wnt/β-catenin signaling, both processes well-described in sustaining chemotherapy resistance, paving the rationale to alternative therapeutic options for T-ALL GC resistant pediatric patients."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • DHCR7 • HMGCS1 • NFATC1 • WNT3A

Gastrodin produces therapeutic effects against preeclampsia by activating Wnt 3a signaling and inhibiting ferroptosis. (PubMed, Exp Cell Res) - "Consistently, Gtd-administration reveals apparent anti-hypertensive effects in a PE-like mouse model with diminished ferroptosis, whereas deactivation of β-catenin by administration with the specific antagonist ICG001 disrupts the protective effects derived from Gtd. Therefore, our results provide an innovative basis for the role of Gtd as a new therapy for PE."

Journal • Gynecology

Piezo1 Mediates Deoxycorticosterone Acetate-Salt Hypertension Through Renal Epithelial Sodium Channel Activation in the Kidneys (KIDNEY WEEK 2025) - "Yoda1 markedly induced increased Na + influx in mpkCCD cells, which was significantly blocked by amiloride. ICG001 significantly attenuated the mechanical force or Yoda1-induced upregulation of β-catenin and ENaC subunits. Conclusion Piezo1 activation induced increased blood pressure likely through upregulating ENaC expression in the kidney of mice with DOCA-salt by activating β-catenin pathway."

Cardiovascular • Hypertension • Nephrology • Renal Disease

Targeting Wnt/β-catenin signaling enhances the efficacy of anti-CD38 immunotherapy in multiple myeloma. (PubMed, Neoplasia) - "These findings demonstrated that targeting Wnt signaling enhances the efficacy of daratumumab and provide a strong rationale for combining daratumumab with Wnt-signaling inhibition as a therapeutic strategy in MM."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

miRNA-195-5p modulates cell proliferation and stemness by targeting the Wnt signalling network in breast cancer. (PubMed, Noncoding RNA Res) - "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."

Journal • Breast Cancer • Oncology • Solid Tumor • CD44 • FZD6 • MIR195 • NANOG • POU5F1 • SOX2

Myogenic induced adipose-derived stem cells sheets combined with electrospun scaffolds of silk fibroin and poly(lactide-co-glycolide) for stress urinary incontinence treatment. (PubMed, J Mol Histol) - "ICG001, a specific inhibitor of β-catenin signaling pathway, could inhibit 5-Aza-induced expression of myoblast genes and proteins...The tissue-engineered sling with MI-ADSCs sheets combined with SF/PLGA can restore leak point pressure (LPP) in the model of SUI steadily. It is of great potential to be a novel tissue-engineered sling in the treatment of SUI."

Journal • Transplantation • Urinary Incontinence • Urology

ACSS3 protein macromolecule regulates glycolysis in keloid through Wnt/β-catenin signaling pathway: Bioinformatics, machine learning, and experimental validation. (PubMed, Cell Signal) - "Conversely, ACSS3 knockdown elicited opposite effects, which were reversed by ICG-001...Additionally, Molecular docking and dynamics simulations were conducted to identify potential drugs targeting ACSS3. In summary, this study demonstrates that ACSS3 modulates aerobic glycolysis and the activity of KFs via the Wnt/β-Catenin pathway, positioning ACSS3 as a promising therapeutic target for keloid treatment."

Journal • Fibrosis

The role of SH3RF2 in lung squamous cell carcinoma and M2 polarization: insights into LZTS2 ubiquitination. (PubMed, Biol Direct) - "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."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Targeted Protein Degradation • CD163 • IL10 • MRC1

Unraveling the role of gut microbiota on the formation of nephrolithiasis: insights from integrated analysis of GWAS, single-cell transcriptomics, bulk RNA sequencing and network Pharmacology. (PubMed, Urolithiasis) - "Drug prediction analysis found that drugs like benzo(a)pyrene could co-target PALLD and R3HDM1, and PALLD had the strongest binding ability with ICG-001, with a binding energy of -9.5 kcal/mol. Finally, fibroblasts (FIBs) and vascular smooth muscle cells/pericytes (VSM/Ps) were determined as key cells, and the expression of PALLD exhibited nonlinear change characteristics during the differentiation process of FIBs and VSM/Ps. PALLD and R3HDM1 were identified as GM-related key genes in nephrolithiasis, providing a reference for exploring the pathogenesis of nephrolithiasis."

Journal • Nephrology • Renal Calculi

Oligodendrocyte-specific Knockout of FPN1 Affects CNS Myelination Defects and Depression-like Behavior in Mice. (PubMed, Free Radic Biol Med) - "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."

Journal • Preclinical • CNS Disorders • Depression • Hematological Disorders • Inflammation • Mood Disorders • Psychiatry • Solid Tumor • IL6 • MBP • OLIG2

Inhibition of Wnt/β-catenin increases anti-tumor activity by synergizing with sorafenib in hepatocellular carcinoma. (PubMed, Cell Death Dis) - "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."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CREBBP • CTNNB1 • MYC

Inter-Relationship Between Melanoma Vemurafenib Tolerance Thresholds and Metabolic Pathway Choice. (PubMed, Cells) - "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."

Journal • Melanoma • Oncology • Solid Tumor • MITF

SALL1 is essential for Histone H3K27 methyltransferase EZH2 to regulates apoptotic responses in renal ischemia/reperfusion injury (ERA 2025) - "The study further reversed the effects of EZH2 silencing by silencing SALL1 or administering the Wnt/β-catenin inhibitor icg001...Finally, the study showed that the EZH2 inhibitor GSK-126 significantly alleviated ischemia/reperfusion-induced AKI. Our results indicate that silencing EZH2 can protect renal function by relieving transcriptional inhibition of SALL1, activating the Wnt/β-catenin pathway, and attenuating tubular epithelial apoptosis response. These results highlight the potential therapeutic value of targeting EZH2 in ischemia/reperfusion-induced AKI."

Acute Kidney Injury • Cardiovascular • Nephrology • Renal Disease • Reperfusion Injury • EZH2

Modulating Wnt/β-catenin pathway activity to enhance chemosensitivity in cholangiocarcinoma. (PubMed, Biomed Pharmacother) - "Inhibiting the Wnt/β-catenin pathway chemosensitizes CCA cells by modulating MOC gene expression. The combination of Wnt/β-catenin inhibitors with chemotherapy may enhance the therapeutic outcomes for CCA patients."

Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

Emergence of the Alveolar Epithelium: A Matter of Time and Tension (ATS 2025) - "Small molecules CHIR and ICG-001 were used in culture to raise and lower β-catenin levels, respectively... No evidence of distal progenitors selecting either AT fate was found until E16.5, at which time we identified a distinct nascent AT2 (nAT2) state that ontology analysis detects upregulation of single-cell migration genes. Resistin-like molecule alpha (RELM-α), a type 2 inflammation regulator, labels nAT2s - which first individually emerged around E16.5 (although instances exist at E15.5) at intermediate zones between the branch tips and stalks of the distal epithelium. Following molecular emergence, we observed nAT2s extruded basally and can subsequently interact with nearby but anatomically distinct lumens, a behavior we provisionally name interlumenal junctioning and whose dynamics we validated by timelapse microscopy."

Inflammation • CTNNB1 • NAT2 • RETN

METTL3 Mediates Wnt/β-Catenin Pathway in Epithelial-Mesenchymal Transition of 16HBE Cells Induced by Beryllium Sulphate. (PubMed, J Appl Toxicol) - "Both METTL3 overexpression and ICG-001 pretreatment mitigated BeSO4-induced EMT and Wnt/β-catenin pathway activation. These findings suggest that METTL3 inhibits BeSO4-induced EMT by suppressing the Wnt/β-catenin pathway, offering novel mechanistic insights into beryllium toxicity and a potential therapeutic target for Be-related pulmonary fibrosis."

Journal • Immunology • Pulmonary Disease • Respiratory Diseases • METTL3

A Phase 2 Trial of Foscenvivint in Liver Cirrhosis Patients Caused by HIV/HCV Co-infection with Hemophilia (OP-724-H201) (clinicaltrials.gov) - P2 | N=6 | Active, not recruiting | Sponsor: Kiminori Kimura, MD | Trial completion date: Jun 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • Fibrosis • Gastroenterology • Hematological Disorders • Hemophilia • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Rare Diseases

Relationship between melanoma vemurafenib tolerance thresholds and metabolic pathway choice and Wnt signaling involvement. (PubMed, bioRxiv) - "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."

Journal • Hematological Disorders • Melanoma • Oncology • Solid Tumor • MITF

Identification biomarkers and therapeutic targets of disulfidptosis-related in rheumatoid arthritis via bioinformatics, molecular dynamics simulation, and experimental validation. (PubMed, Sci Rep) - "Finally, the RT-qPCR results showed that OXSM was significantly increased in the peripheral blood of RA patients compared with healthy controls, consistent with the bioinformatics analysis. These studies suggest that OXSM may be a potential biomarker and therapeutic target for diagnosing RA, and ICG 001 may be a potential drug for RA. These findings may provide new avenues for the effective diagnosis and treatment of RA."

Biomarker • Journal • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology

Long-term exposure of indoxyl sulfate induces mesothelial-to-mesenchymal transition of peritoneal mesothelial cells via β-catenin-involved signaling pathway. (PubMed, Adv Clin Exp Med) - "Indoxyl sulfate induces MMT in human peritoneal mesothelial cells, and these changes can be reversed by the specific β-catenin inhibitor ICG-001. This suggests that IS may be considered as another inducer of MMT during PD through the β-catenin signaling pathway."

Journal • Diabetes • CDH1

Effects of ADRM1 on osteoblast differentiation and mineralization in osteoporosis. (PubMed, Am J Transl Res) - "Our findings suggest that silencing ADRM1 induces osteoblast mineralization and differentiation by activating the Wnt/β-catenin pathway. This finding underscores the therapeutic potential of the ADRM1/Wnt/β-catenin axis in treating OP."

Journal • Osteoporosis • Rheumatology • ADRM1

Modulating Wnt/"beta"-catenin pathway activity as a potential chemosensitive strategy in cholangiocarcinoma (LCS 2025) - " In vitro assays were performed using intrahepatic (CC-LP1, CC-SWI and HuCCT1) and extrahepatic CCA cell lines (EGI-1 and TFK-1) treated with Wnt/"beta"-catenin pathway inhibitors (C59, XAV939 or PRI724) to evaluate, by RT-qPCR and WB, expression of Wnt target genes and genes involved in MDR...Following 72h of treatment with Wnt/"beta"-catenin inhibitors, both alone or in combination with antitumor drugs (cisplatin, gemcitabine, and 5-FU), cell viability was determined by MTT test... Inhibition of the Wnt/"beta"-catenin signaling pathway induces chemosensitization of CCA cells by changing the expression of several MOC genes. The use of therapeutic strategies combining Wnt/"beta"-catenin pathway inhibition with chemotherapy may provide a pharmacological advantage in treating CCA patients."

Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • BIRC5

A Phase 2 Trial of Foscenvivint in Liver Cirrhosis Patients Caused by HIV/HCV Co-infection With Hemophilia (OP-724-H201) (clinicaltrials.gov) - P2 | N=6 | Active, not recruiting | Sponsor: Kiminori Kimura, MD | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Gastroenterology • Hematological Disorders • Hemophilia • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Rare Diseases