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

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

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

Wnt/β-Catenin Pathway-Mediated PD-L1 Overexpression Facilitates the Resistance of Non-Small Cell Lung Cancer Cells to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. (PubMed, Discov Med) - "Activation of the Wnt/β-catenin pathway mediates the high expression of PD-L1 to promote the resistance of NSCLC cells to icotinib. Thus, targeted inhibition of PD-L1 expression is of benefit for the treatment of NSCLC."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MMP2 • MMP9 • PD-L1

Molecular Interactions of the Plant Steroid Hormone Epibrassinolide on Human Drug-Sensitive and Drug-Resistant Small-Cell Lung Carcinoma Cells. (PubMed, Cancers (Basel)) - " Pharmacologic interactions between EB and the Wnt signaling inhibitors IGC-011 and PRI-724 were determined by the combination index method and showed antagonism, indicating that EB acts on the same pathway as these inhibitors...Following exposure to human liver microsomes, EB was metabolized by NADPH-dependent oxidation and UDPG-dependent glucuronidation, as evidenced by the elimination of EB cytotoxicity against SCLC cells. Taken together, these data indicate that EB, a steroid hormone in plants consumed in the human diet, is pharmacologically active in drug-sensitive and drug-resistant SCLC cells in the Wnt signaling pathway, alters apoptotic gene expression, and is a substrate for microsomal modifications."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • BIRC5 • CASP3 • CAV1 • MYCL

The Wnt/Pyruvate kinase, Muscle axis plays an essential role in the differentiation of mouse neuroblastoma cells. (PubMed, Neurochem Int) - "The Wnt inhibitor ICG-001 and PKM activator ML-265 inhibited ATRA-induced Neuro-2a and N1E-115 differentiation, whereas RNA interference-mediated Pkm silencing promoted Neuro-2a and N1E-115 differentiation, which was reversed by PKM overexpression...These results indicate that Wnt/β-catenin signaling promotes Neuro-2a and N1E-115 differentiation by inhibiting PKM-mediated glycolysis during ATRA-induced differentiation. These findings may provide a new theoretical basis for the role of glycolysis in nerve differentiation."

Journal • Preclinical • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • PKM

Exploiting potential molecular compounds for treating testicular seminoma by targeting immune related genes. (PubMed, Cell Commun Signal) - "The signature initially constructed based on immune-related genes shows promise for predicting outcomes and assessing the efficacy of immunotherapy in seminoma patients. Rutin, ICG-001, and Doxorubicin have demonstrated potential to target these signature genes and inhibit tumor cell viability."

IO biomarker • Journal • Germ Cell Tumors • Oncology • Testicular Cancer • Testicular Seminoma

SALL1 Is Essential for Histone H3K27 Methyltransferase EZH2 to Regulate Apoptotic Responses in Kidney Ischemia-Reperfusion Injury (KIDNEY WEEK 2024) - "The study further reversed the effects of EZH2 silencing by silencing SALL1 or administering the Wnt/β-catenin inhibitor icg001. 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

AN ORAL INHIBITOR OF CBP/Β-CATENIN SIGNALING, C-82, IMPROVES LIVER STEATOSIS, FUNCTION, INFLAMMATION AND FIBROSIS IN THE GAN DIET-INDUCED OBESE MOUSE MODEL OF MASH (AASLD 2024) - "We previously reported the efficacy of PRI-724, a second-generation specific CBP/β-catenin antagonist, for HCV/HBV cirrhosis... C-82 treatment improves not only MASH-like liver disorders (steatosis, function and inflammation) but also liver fibrosis. C-82, an oral inhibitor of CBP/β-catenin signaling, shows a potent therapeutic effect on MASH-related liver fibrosis and steatosis."

Preclinical • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • PDK4

Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through β-catenin/CREB interruption. (PubMed, Acta Pharm Sin B) - "To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001...Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions."

Journal • Metastases • Oncology • CTNNB1

Tenascin-C induces transdifferentiation of retinal pigment epithelial cells in proliferative vitreoretinopathy. (PubMed, Exp Eye Res) - "ICG-001, a β-catenin inhibitor, efficiently attenuated PVR progression in a PVR animal model. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of PVR via the integrin αV and β-catenin pathways. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of epiretinal membrane development associated with PVR."

Journal • Retinal Disorders • TGFB1

Combined targeting of Hedgehog/GLI1 and Wnt/β-catenin pathways in mantle cell lymphoma. (PubMed, Hematol Oncol) - "Moreover, GLI1 knockdown combined with ICG-001 synergistically induced apoptosis and increased drug sensitivity of MCL cells to doxorubicin and ibrutinib. Overall, the combined targeting of both the Hh/GLI1 and Wnt/β-catenin pathways was more effective in suppressing proliferation, inducing G0/G1 cycle retardation, promoting apoptosis, and increasing drug sensitivity of MCL cells than mono treatments. These findings emphasize the potential of combinatorial therapy for treating MCL patients."

Journal • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • GLI1

A novel drug prejudice scaffold-imidazopyridine-conjugate can promote cell death in a colorectal cancer model by binding to β-catenin and suppressing the Wnt signaling pathway. (PubMed, J Adv Res) - "CHL-C is capable of inducing apoptosis and autophagy by influencing the Wnt/β-catenin signaling pathway."

Journal • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ANXA5 • AXIN1 • WNT3A

PFDA promotes cancer metastasis through macrophage M2 polarization mediated by Wnt/β-catenin signaling. (PubMed, Chemosphere) - "Furthermore, in vivo studies corroborated that PFDA-pretreated RAW264.7 could promote tumor metastasis, which could be mitigated by pretreatment with the β-catenin inhibitor ICG001. In conclusion, our study demonstrated that PFDA could promote cancer metastasis through regulating macrophage M2 polarization in a Wnt/β-catenin-dependent manner."

Journal • Oncology • Ovarian Cancer • Solid Tumor

AQP5 promotes epithelial-mesenchymal transition and tumor growth through activating the Wnt/β-catenin pathway in triple-negative breast cancer. (PubMed, Mutat Res) - "In the TNBC cells, AQP5 modulates the expression levels of EMT-related proteins through activation of Wnt/β-catenin signaling pathway, thus enhancing the cell proliferation, migration and invasion while inhibiting the cell apoptosis."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AQP3 • BCL2 • CASP3

Activation of Wnt/β-catenin signaling promotes immune evasion via the β-catenin/IKZF1/CCL5 axis in hepatocellular carcinoma. (PubMed, Int Immunopharmacol) - "In conclusion, our findings suggest that combined application of ICG-001 and anti-PD-1 antibody exhibits significantly enhanced antitumor efficacy. Hence, combining a WNT/β-catenin signaling pathway inhibitor with anti-PD-1 therapy may be a promising treatment strategy for patients with HCC."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CCL5 • CCR5 • CD8 • IKZF1

3D Chromatin Alteration by Disrupting β-Catenin/CBP Interaction Is Enriched with Insulin Signaling in Pancreatic Cancer. (PubMed, Cancers (Basel)) - "The therapeutic potential of targeting the β-catenin/CBP interaction has been demonstrated in a variety of preclinical tumor models with a small molecule inhibitor, ICG-001, characterized as a β-catenin/CBP antagonist...We finally elicit the deletion of a looping of IRS1-a key insulin signaling gene-significantly impeding pancreatic cancer cell growth, indicating that looping-mediated insulin signaling might act as an oncogenic pathway to promote pancreatic cancer progression. Our work shows that targeting aberrant insulin chromatin looping in pancreatic cancer might provide a therapeutic benefit."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CTNNB1

TRIM26 deficiency enhancing liver regeneration through macrophage polarization and β-catenin pathway activation. (PubMed, Cell Death Dis) - "Pharmacological inhibition of Wnt/β-catenin pathway by ICG-001 or depletion of macrophages by clodronate liposomes diminishes the pro-regenerative effects of Trim26 deficiency. Moreover, bone marrow transplantation experiments provide evidence that Trim26 knockout in myeloid cells alone can also promote liver regeneration, highlighting the critical role of macrophage Trim26 in this process. Taken together, our study uncovers TRIM26 as a negative regulator of liver regeneration by modulating macrophage polarization and Wnt/β-catenin signaling in hepatocytes, providing a potential therapeutic target for promoting liver regeneration in clinical settings."

Journal • Bone Marrow Transplantation • Hepatology • Liver Failure • Targeted Protein Degradation • Transplantation • WNT2

Mechanism of electroacupuncture in treating uterine endometrial fibrosis in intrauterine adhesions rats based on Wnt/β-catenin pathway-mediated epithelial-mesenchymal transition. (PubMed, Zhen Ci Yan Jiu) - "EA may reverse the EMT process and reduce the degree of fibrosis in endometrial tissue by inhibiting the Wnt/β-catenin signaling pathway, thereby promoting the repair of endometrial damage in IUA."

Journal • Preclinical • Fibrosis • Immunology • Infectious Disease • CDH1 • CDH2 • CTGF • TGFB1 • VIM

Escherichia coli infection induces ferroptosis in bovine mammary epithelial cells by activating the Wnt/β-catenin pathway-mediated mitophagy. (PubMed, Mitochondrion) - "Rapamycin and chloroquine increased and suppressed ferroptosis, respectively, in E. coli-treated bMECs. Moreover, E. coli infection activated the Wnt/β-catenin pathway, but foscenvivint alleviated it. In conclusion, E. coli infection induced ferroptosis through activation of the Wnt/β-catenin pathway-promoted mitophagy, and it also suppressed GPX4 expression."

Journal • Hematological Disorders • Infectious Disease • GPX4