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

Histone demethylase JMJD2D promotes lung cancer progression by activating Wnt/β-catenin signaling. (PubMed, Cell Signal) - "PRI-724 or Z-JIB-04 treatment conditions were associated with lower malignancy-associated readouts and lower levels of selected transcripts, without an apparent change in total β-catenin abundance. These findings associate JMJD2D with aggressive clinical and experimental phenotypes in lung cancer and support further investigation of its molecular role and therapeutic relevance."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCND1 • CTNNB1 • KDM4D • MMP2 • MMP9

Viral exploitation of p300/CBP at the virus-cancer interface: Chromatin regulation, oncogenesis, immune evasion, and therapeutic targeting. (PubMed, Cancer Treat Res Commun) - "Preclinical studies support catalytic, interaction-selective, and virus-specific targeting strategies, but human evidence is limited to early-phase PRI-724/OP-724 antifibrotic studies in viral cirrhosis. Because p300/CBP also support normal transcription and antiviral immunity, systemic inhibition may cause substantial toxicity. Overall, p300/CBP are best viewed as context-dependent regulatory hubs, and translation will require paralog-, domain-, and disease-specific validation."

Journal • Review • Fibrosis • Immunology • Oncology • CREBBP

Elucidating the molecular basis of ATP synthase inhibition: A virtual screening framework for next-gen selective acaricides. (PubMed, Sci Adv) - "Using these mechanistic insights, we developed a structure-based virtual screening pipeline to identify selective small-molecule inhibitors, including Vepdegestrant (ARV-471) and ICG-001, that exploit binding-site variation to achieve robust species specificity. This target-centric discovery framework not only advances the mechanistic understanding of ATP synthase inhibition but also establishes a scalable strategy for the rational design of environmentally safe and precision-oriented acaricides."

Journal

Somatic Stem Cells: Control of Quiescence Versus Activation in Aging and Cancer. (PubMed, Cancers (Basel)) - "Based on over 25 years of chemical genetic and genetic investigation, we discuss the differential roles of the two Kat3 coactivators (Kat3A/CREBBP/CBP and Kat3B/EP300/p300) in regulating stem cell quiescence and the mode of division of activated stem cells. The ability to pharmacologically regulate differential Kat3 coactivator usage has important implications to ameliorate the aging process as well as to eliminate quiescent cancer stem cells, which are the cause of disease relapse and metastasis."

Journal • CNS Disorders • Fibrosis • Immunology • Oncology • Sarcopenia • CREBBP • EP300

NR4A1 Regulates Glycolysis in M1 Macrophages via the Wnt/β-Catenin Pathway to Affect Sepsis-Induced Myocardial Injury. (PubMed, J Inflamm Res) - "Moreover, inhibition of the Wnt/β-catenin pathway with ICG-001 in the LPS+oe-NR4A1 group increased the expression of M1 macrophage markers and enhanced glycolysis, while reduced cardiomyocyte activity. In summary, high expression of NR4A1 inhibits glycolysis in macrophages by activating the Wnt/β-catenin pathway, thereby affecting cardiomyocyte apoptosis mediated by M1 macrophage polarization."

Journal • Infectious Disease • Septic Shock • NR4A1 • SLC2A1

Paeonol induces osteoblast differentiation of bone marrow-derived human mesenchymal stromal cells and inhibits adipocyte differentiation. (PubMed, Tissue Cell) - "Our in vitro findings demonstrate that paeonol promotes osteoblast differentiation and inhibits adipocyte differentiation in hBM-MSCs. These effects are linked to the modulation of Wnt/BMP and AMPK signaling pathways, respectively."

Journal • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • BMP2 • CEBPA • CTNNB1 • FASN • PPARG • RUNX2 • SMAD1

OP-724-H202: A Phase 2 Study of Foscenvivint in Liver Cirrhosis Patients Caused by HIV/HCV Co-infection With Hemophilia (clinicaltrials.gov) - P2 | N=4 | Recruiting | Sponsor: Kiminori Kimura, MD | Not yet recruiting ➔ Recruiting

Enrollment open • Fibrosis • Gastroenterology • Hematological Disorders • Hemophilia • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Rare Diseases • CD4

Inhibition of Stemness Pathways during Acute SIV Limits Infection of Central Memory CD4+ T Cells and Alters Viral Reservoir Activity in Macaques. (PubMed, bioRxiv) - "Following sustained ART, levels of SIV RNA in CD4+ T cells were higher in the PRI-724 + LY3039478-treated group compared to controls, although SIV DNA was similar. These findings suggest that stemness pathway inhibition promotes memory T cell differentiation leading to a more transcriptionally active reservoir and has potential to synergize with "shock-and-kill" approaches to reduce HIV persistence."

Journal • Human Immunodeficiency Virus • Infectious Disease • CD4

OP-724-H202: A Phase 2 Study of Foscenvivint in Liver Cirrhosis Patients Caused by HIV/HCV Co-infection With Hemophilia (clinicaltrials.gov) - P2 | N=4 | Not yet recruiting | Sponsor: Kiminori Kimura, MD

New P2 trial • Fibrosis • Gastroenterology • Hematological Disorders • Hemophilia • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Rare Diseases • CD4

Beyond the target: implications of Wnt pathway inhibitors on bone health. (PubMed, J Mol Med (Berl)) - "We found that inhibitors targeting upstream components of the pathway-such as Wnt ligands or receptors (e.g., porcupine inhibitors, Ipafricept, or Vantictumab)-frequently lead to bone-related adverse effects, including fractures and early trial termination...In contrast, downstream inhibitors (e.g., PRI-724, niclosamide) have not been linked to bone toxicity, although this may reflect either underreporting or a genuinely lower skeletal impact. Further preclinical studies are warranted to better understand these differential effects. A thorough understanding of bone-specific risks is critical as Wnt signaling inhibitors continue to advance in clinical development."

Journal • Review • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Musculoskeletal Diseases • Oncology • Orthopedics

Src and β-catenin control a senescence-fibrotic phenotype in uterine fibroid cells. (PubMed, Sci Rep) - "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."

Journal • Fibrosis • Gynecology • Immunology • Infertility • Musculoskeletal Pain • Oncology • Pain • Sexual Disorders • Solid Tumor • Uterine Leiomyoma • Women's Health • CCND1 • CDKN1A • CTGF • CTNNB1

Pyraclostrobin Exposure Triggers Renal Injury by Activating Wnt/β-Catenin Signaling Pathway-Mediated Renal Fibrosis in Mice. (PubMed, J Appl Toxicol) - "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."

Journal • Preclinical • Fibrosis • Immunology • Inflammation • Oncology • Renal Disease • CCND1 • CTGF • IL10 • IL1B • IL6 • KIM1 • LCN2 • MYC • TGFB1 • TNFA

Targeting barrier integrity: Pseudoginsenoside RT2 ameliorates ulcerative colitis by driving epithelial renewal via the Wnt/β-catenin pathway. (PubMed, Phytomedicine) - "RT2 attenuates UC by activating Wnt/β‑catenin pathway, thereby restoring intestinal barrier integrity via driving epithelial renewal, with efficacy comparable to the positive control drug SASP. RT2 represents a promising natural product candidate for UC treatment."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • LGR5

Ductal epithelial MXD3 promotes disease progression in acute pancreatitis through Wnt/β-catenin-mediated inflammation and injury. (PubMed, Front Physiol) - "Furthermore, functional rescue experiments confirmed the pathway's necessity, wherein the β-catenin inhibitor ICG-001 substantially reversed MXD3-driven apoptosis, necrosis, and pro-inflammatory cytokine secretion (IL-1β, IL-6, MCP-1) in vitro. Our findings establish a novel MXD3- Wnt/β-catenin axis as a crucial mechanism governing epithelial pathology in AP, revealing MXD3 as a promising therapeutic target for this debilitating condition."

Journal • Fibrosis • Immunology • Inflammation • Pancreatitis • CCND1 • CTNNB1 • IL1B • IL6 • MYC • TNFA

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=5 | Completed | Sponsor: Kiminori Kimura, MD | Active, not recruiting ➔ Completed

Trial completion • Fibrosis • Gastroenterology • Hematological Disorders • Hemophilia • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Liver Cirrhosis • Rare Diseases • CD4

Integrative systems biology and drug repurposing reveal key regulatory hubs and a prognostic signature in gastric cancer. (PubMed, Discov Oncol) - "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."

Journal • Gastric Cancer • Oncology • Solid Tumor • CDC37 • CTNNB1 • HSP90AB1 • SRSF7

Role of the cross-regulation between Wnt pathway activation and androgen receptor signaling in prostate cancer treatment resistance. (PubMed, Cell Death Differ) - "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."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • RNF43 • ZNRF3

Overexpressed CPAP promotes cancer stemness and enhances chemo-resistance in HCC (AACR 2024) - "Combined treatment with sorafenib and Wnt/β-catenin pathway inhibitor PRI-724 significantly inhibited CPAP-overexpressing Hep3B spheroids-derived tumor growth in a xenograft mouse model. Our study highlights the oncogenic role of CPAP in promoting CSCs-induced sorafenib resistance in HCC and provides insights into potential therapeutic strategies."

Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • ABCG2 • CD24 • STAT3

Targeting the β-catenin signaling axis in osteosarcoma (AACR 2024) - "In silico docking studies suggested that PCT may have similar anti-cancer effect compared to β-catenin inhibitors (e.g., MSAB, ICG001)...In summary, our findings indicate that PCT exhibits therapeutic potential against osteosarcoma by targeting the β-catenin pathway. Further mechanistic studies are currently underway in our lab."

Oncology • Osteosarcoma • Sarcoma • Solid Tumor • AXL

BRISC Deficiency Drives Heart Failure by Regulating β-Catenin K63 Ubiquitination. (PubMed, Hypertension) - "Pharmacological inhibition of β-catenin with ICG-001 effectively rescued hypertensive cardiac remodeling and dysfunction caused by Abro1 deficiency. BRISC acts as a critical K63-specific deubiquitinase that preserves cardiac homeostasis by restraining β-catenin overactivation. Targeting the BRISC-β-catenin axis may represent a novel therapeutic strategy for hypertensive heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Targeted Protein Degradation • CTNNB1

ATP-binding cassette subfamily A member 5 suppresses pancreatic ductal adenocarcinoma progression and chemoresistance by promoting β-catenin ubiquitin-dependent degradation. (PubMed, Drug Resist Updat) - "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."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Targeted Protein Degradation • ABCA5 • CTNNB1

Protecting the Heart Against Anthracyclines: The Elusive Search for the Optimal Cardiomyocyte Model. (PubMed, JACC Basic Transl Sci) - No abstract available

Journal • Cardiovascular

Mesenchymal stem cell-derived exosomes rescue stress-dependent morphological deficits in primary hippocampal neurons via Wnt5a/β-catenin/WAVE2 pathway. (PubMed, Brain Res) - "Our study indicate that MSC-Exos ameliorate stress-dependent morphological deficits in primary hippocampal neurons via the exosomal Wnt5a/β-catenin/WAVE2 pathway."

Journal • CCND3 • CDH2

Danggui-Baishao herb pair protects against dextran sulfate sodium-induced colitis by modulating the Wnt/β-catenin pathway. (PubMed, World J Gastroenterol) - "The herb pair effectively reduces colonic inflammation and maintains the integrity of the intestinal barrier. Moreover, the anti-colitis efficacy of the herb pair is closely associated with activation of the Wnt/β-catenin pathway."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Regulatory Signaling Pathways in Ovarian Cancer Stem Cells: Their Role in Tumor Progression and Therapeutic Strategies. (PubMed, Iran Biomed J) - "Various therapeutic agents have been studied to target these pathways in OCSCs, including γ-secretase inhibitors (nirogacestat), smoothened inhibitors (vismodegib and sonidegib), and Wnt/β-catenin inhibitors (PRI-724 and ipafricept). To improve treatment outcomes, strategies involving combination approaches and personalized treatments need to be explored. This review aims to summarize current evidence on the role of Wnt/β-catenin, Notch, and Hedgehog signaling pathways in OCSCs and their therapeutic implications in ovarian cancer."

Journal • Oncology • Ovarian Cancer • Solid Tumor