XAV-939 / Novartis - LARVOL DELTA

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

Interfering with AQP1 alleviates ferroptosis, improves mitochondrial function and energy metabolic disorder in hypoxia/reoxygenation-induced H9c2 cardiomyocytes via Wnt/β-catenin pathway. (PubMed, Microvasc Res) - "Further, AQP1 deletion might activate Wnt/β-catenin pathway and XAV939, an inhibitor of Wnt signaling pathway could partially revert the influences of AQP1 knockdown on the viability, mitochondrial function, ferroptosis and energy metabolism in H/R-treated H9c2 cells. To be concluded, AQP1 interference might protect against H/R-induced mitochondrial dysfunction, ferroptosis and energy metabolism disorder in H9c2 cells via modulating Wnt/β-catenin pathway."

Journal • Cardiovascular • Coronary Artery Disease • Hematological Disorders • Metabolic Disorders • Myocardial Ischemia • Reperfusion Injury • AQP1

Targeting of the IL-33/Wnt axis restricts breast cancer stemness and metastasis. (PubMed, Sci Rep) - "Mechanistically, IL-33 activated Wnt/β-catenin signaling to promote stemness, which was reversed by the Wnt inhibitor XAV-939...Our findings establish an IL-33-Wnt axis as a critical driver of breast cancer aggressiveness and propose AAV-mediated ST2 silencing as a novel therapeutic strategy. Targeting this axis may offer dual benefits by suppressing stemness and enhancing immune surveillance, warranting clinical exploration for advanced breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • ALDH1A1 • CD44 • IL33

Establishment of bovine extraembryonic endoderm stem cells enables efficient blastoid formation. (PubMed, Cell Rep) - "Here, we report that a chemical cocktail (FGF4, BMP4, IL-6, XAV939, and A83-01) enables the de novo derivation and long-term culture of bovine XENs (bXENs) from blastocysts...Finally, 3D assembly of bXENs with bovine EPSCs and trophoblast stem cells enables efficient generation of blastoids that resemble blastocysts. bXENs and blastoids established here represent accessible in vitro models for understanding embryogenesis and improving reproductive efficiency in domestic livestock."

Journal • BMP4 • FGF4 • IL6

Biodentine Counteracts the Aging Process of Human Dental Pulp Stem Cells Through Wnt/β-Catenin Pathway. (PubMed, Int Dent J) - "The study demonstrated that Biodentine promotes proliferation and exerts anti-aging effects on hDPSCs through the Wnt/β-catenin pathway."

Journal

Paclitaxel alleviates spinal cord injury via activation of the Wnt/β-catenin signaling pathway. (PubMed, Mol Med) - "This study provides important new mechanistic insight on the beneficial effects of PTX in protecting against spinal cord injury, as well as the experimental basis for its potential therapeutic use."

Journal • CNS Disorders • Fibrosis • Immunology • Muscular Atrophy • Orthopedics

Nesuparib, a dual inhibitor of PARP and tankyrase, is efficacious in preclinical gastric cancer models by regulation of HIPPO and Wnt pathway (AACR 2025) - "To evaluate the impact of nesuparib on cell growth, half maximal inhibitory concentration (IC50) of nesuparib, Olaparib, and XAV939 in clonogenicity was compared in BRCA wild type gastric cancer cells. In addition, the combination of nesuparib with irinotecan showed stronger tumor growth suppression than the combination of Olaparib with irinotecan.In summary, these results suggest that nesuparib may exert anti-tumor efficacy in specific types of cancers with pro-cancerous signaling of the Wnt or Hippo pathway by the regulation of TNKS. This warrants a proof-of-concept of anti-tumor effect of nesuparib in gastric cancers and its potentials for clinical benefits."

Preclinical • Gastric Cancer • Oncology • Solid Tumor • AXIN1 • BRCA • CCND1 • MYC

Glycyrrhizic acid promotes liver regeneration through activating β-catenin in acetaminophen-induced liver injury. (PubMed, J Ethnopharmacol) - "GA alleviates APAP-induced acute liver injury and significantly promotes liver regeneration following APAP-induced liver damage. The mechanism underlying these effects may involve the activation of the β-catenin signaling pathway, which in turn promotes hepatocyte proliferation and thereby mitigates APAP-induced acute liver injury. This highlights GA's role in liver regeneration and its promise as a therapeutic strategy for hepatoprotection."

Journal • Hepatology • Liver Failure • CCND1 • CDK4 • PCNA

Stage-dependent proteomic alterations in aqueous humor of diabetic retinopathy patients based on data-independent acquisition and parallel reaction monitoring. (PubMed, J Transl Med) - "This study established a comprehensive AH proteomic signature of DR progression, offering insights into the pathogenesis of DR and highlighting potential biomarkers and novel therapeutic targets."

Biomarker • Journal • Cataract • Diabetes • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Retinal Disorders • Type 2 Diabetes Mellitus • RBP4 • SPP1

Generation of human induced pluripotent stem cell-derived cortical neurons expressing the six tau isoforms. (PubMed, J Alzheimers Dis) - "Most importantly, the six Tau isoforms were expressed from day 80 in a developmentally regulated manner, modeling the situation in human brains on an accelerated timeline.ConclusionsThis chemically defined differentiation method produces a key hallmark of mature human cortical neurons by expressing the six main splicing isoforms of Tau. It will greatly facilitate disease modeling and therapeutic discovery for many human brain disorders involving cortical neurons."

Journal • Alzheimer's Disease • CNS Disorders • MAPT

Interactions of tumor necrosis factor receptor-associated factor 4 and pyruvate kinase muscle isoform 2 promote malignant behavior and aerobic glycolysis in colorectal cancer cells. (PubMed, Cytojournal) - "Notably, the effects of TRAF4 or PKM2 overexpression on cell malignant behavior, glucose uptake, lactate production, and GLUT1, PKM2, HK2, and LDHA protein expression levels were partially offset by the Wnt/β-catenin signaling suppressor XAV939 (P < 0.05, P < 0.01, P < 0.001, and P < 0.0001). TRAF4 and PKM2 are associated with CRC development. TRAF4 binds to PKM2 and promotes CRC malignant behavior and glycolysis through the Wnt/β-catenin signaling pathway."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HK2 • LDHA • PKM • SLC2A1 • TNFA • TRAF4

In silico and in vitro analysis of imiquimod as a potential tankyrase 2 inhibitor in wnt-active cancers [WITHDRAWN] (AACR 2025) - "Cavity-guided blind docking using the CB Dock 2 program showed that imiquimod shared up to 16 amino acid residues in the binding pocket of TNKS2 when compared with the binding of a commercial TNKS inhibitor, XAV939. In vitro studies using Wnt-active cancer cell lines are currently underway to probe the predicted in silico results. This is the first study that proposes a novel potential anticancer mechanism of Imiquimod through Wnt pathway inhibition."

Preclinical • Gastric Cancer • Oncology • Solid Tumor • PARP1 • TNKS2

β-catenin-mediated aerobic glycolysis: a marker of poor prognosis in triple-negative breast cancer (AACR 2025) - "In conclusion, this study is the first to identify a novel β-catenin-regulated aerobic glycolysis pathway in triple-negative breast cancer (TNBC). We also demonstrated that Axitinib is a more effective inhibitor of this pathway than XAV939."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTNNB1 • LDHA • PFKP • SLC16A1

Deciphering the interplay of β-catenin/YAP signaling and alveolar lineage plasticity during targeted therapy in non-small cell lung cancer (AACR 2025) - "Disrupting the expression and stability of the β-catenin/YAP complex, either through knockdown of these genes or by using Tankyrase inhibitors (e.g. XAV-939 or IWR1) to regulate the β-catenin destruction complex, re-sensitized DTP cells to the EGFR inhibitor Osimertinib. Our findings shed light on the interplay between β-catenin/YAP signaling and alveolar cell-like lineage signatures in residual cancer states. By targeting this axis, we propose a novel therapeutic approach to overcome drug tolerance and improve clinical outcomes for patients with NSCLC undergoing targeted therapy."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FZD2 • WNT3A

Targeting POU5F1-expressing circulating tumor cells to prevent metastasis and recurrence in colorectal cancer (AACR 2025) - "POU5F1-expressing cells are critical drivers of CRC metastasis and recurrence, exhibiting stem-like properties and treatment resistance. Their enrichment in Wnt signaling and CTLA4 expression identifies actionable therapeutic targets. Our findings highlight the potential of Wnt/β-catenin inhibitors like XAV939 to prevent CRC metastasis and recurrence, paving the way for improved therapeutic strategies in high-risk patients."

Circulating tumor cells • IO biomarker • Tumor cell • Colorectal Cancer • Oncology • Solid Tumor • CTCs • CTLA4 • POU5F1

Elucidation of novel β-catenin-driven aerobic glycolysis pathway in Triple Negative Breast Cancers (GBCC 2025) - "In conclusion, this study is the first to identify a novel β-catenin-regulated aerobic glycolysis pathway in TNBC, demonstrating that Axitinib is a more effective inhibitor of this pathway, compared to XAV939."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTNNB1 • LDHA • PFKP • SLC16A1

14,15-EET Maintains Mitochondrial Homeostasis to Inhibit Neuronal Pyroptosis After Ischemic Stroke. (PubMed, Stroke) - "The WNT signaling pathway inhibitor XAV-939 reduced the expression of mitophagy protein Parkin and upregulated the expression of caspase-1 and GSDMD in HT22 cells with oxygen-glucose deprivation/reoxygenation and 14,15-EET treatment. 14,15-EET regulates mitochondrial homeostasis to inhibit neuronal pyroptosis, thereby promoting the recovery of neurological function in mice after cerebral ischemia-reperfusion. These results provide new ideas for maintaining mitochondrial homeostasis and inhibiting neuronal pyroptosis after cerebral ischemia-reperfusion."

Journal • Cardiovascular • Ischemic stroke • Reperfusion Injury • CTNNB1 • NLRP1 • WNT3A

Small molecules direct the generation of ameloblast-like cells from human embryonic stem cells. (PubMed, Stem Cell Res Ther) - "We established an efficient small molecule-based method to differentiate hESCs into ameloblast-like cells through the concerted modulation of RA, BMP, WNT, and NOTCH signaling pathways, potentially advancing research in enamel and tooth regeneration."

Journal • AMBN

Naringin promotes osteoblast differentiation and ameliorates osteoporosis in ovariectomized mice. (PubMed, Sci Rep) - "Notably, naringin antagonized the inhibitory effects of XAV939 (a Wnt/β-catenin pathway inhibitor) on OPN, COL1A1, and RUNX2 protein expression. These findings demonstrate that naringin enhances bone density in OVX mice and promotes osteogenic differentiation of MC3T3-E1 cells via activation of the Wnt/β-catenin pathway."

Journal • Preclinical • Osteoporosis • Rheumatology • COL1A1 • RUNX2 • WNT3A

Downregulation of PD-L1 expression by Wnt pathway inhibition to enhance PD-1 blockade efficacy in hepatocellular carcinoma. (PubMed, Biol Direct) - "Inhibition of the Wnt pathway reduced PD-L1 expression in HCC cells and enhanced the efficacy of PD-L1 blockade, supporting its potential as HCC treatment."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CTNNB1 • EIF4E • EIF4EBP1 • PD-L1

Developmental overproduction of cortical superficial neurons impairs adult auditory cortical processing. (PubMed, Sci Rep) - "Altogether, our results suggest that abnormal auditory cortical processing contributes to the atypical auditory detectability in XAV939-treated mice. Although the expansion of cortical size is evolutionarily advantageous, an abnormal expansion during development can result in detrimental effects on cortical processing and perceptual behavior in adulthood."

Journal • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Psychiatry

Activated Notch1 promotes macrophage polarization and exacerbates sepsis-induced acute lung injury via β-catenin/NF-κB signaling. (PubMed, Biochem Pharmacol) - "In this study, we constructed myeloid-specific Notch1 knockout mice, overexpressed the Notch intracellular domain (NICD), and inhibited β-catenin using XAV939 to investigate the impact and mechanisms of Notch1 regulation in macrophage polarization and inflammatory responses in cecal ligation and puncture (CLP)-induced septic mice...Specifically, NICD interacts with β-catenin in macrophages, amplifying NF-κB activation and its nuclear translocation. These results demonstrate that the Notch1 signaling pathway plays a pivotal role in regulating macrophage phenotypic switching, highlighting its potential as a therapeutic target for attenuating sepsis-associated ALI through immune homeostasis restoration."

Journal • Acute Lung Injury • Infectious Disease • Inflammation • Respiratory Diseases • Septic Shock • NICD • NOTCH1

Blue light-emitting diode promotes mineralization of stem cells from the apical papilla via cryptochrome 1/Wnt/β-catenin signaling. (PubMed, J Mol Histol) - "Additionally, the Wnt/β-catenin pathway was analyzed using specific inhibitors (XAV-939) to elucidate the underlying molecular mechanisms...Blue LED light at 4 J/cm2 enhances SCAPs mineralization by modulating CRY1 expression and activating the Wnt/β-catenin pathway. These findings provide mechanistic insights into photobiomodulation (PBM) in bone regeneration and highlight its potential for tissue engineering and regenerative medicine."

Journal • CRY1 • RUNX2

Pre-ischaemic empagliflozin treatment attenuates blood-brain barrier disruption via β-catenin mediated protection of cerebral endothelial cells. (PubMed, Cardiovasc Res) - "EMPA administration before tMCAO attenuated ischaemia/reperfusion-induced BBB disruption and inflammation via β-catenin-mediated protection of cerebral microvascular endothelial cells. Therefore, EMPA shows potential for improving stroke outcomes as an adjunctive preventive strategy."

Journal • Cardiovascular • Inflammation • Ischemic stroke • Reperfusion Injury • Targeted Protein Degradation • CTNNB1

Upregulated TCF1+ Treg Cells With Stronger Function in Systemic Lupus Erythematosus Through Activation of the Wnt-β-Catenin. (PubMed, Immunology) - "The addition of XAV939 impaired the function of TCF1+ Treg cells. Clinically, TCF1+ Treg cells were not only related to CRP, ESR and IL-2, but also could differentiate SLE patients from healthy controls, primary Sjögren's syndrome patients and rheumatoid arthritis patients. In conclusion, the increased TCF1+ Treg cells in SLE patients indicate a stronger suppressive function for the activated Wnt-β-catenin pathway and help screening and assisting in the diagnosis of SLE patients."

IO biomarker • Journal • Immunology • Inflammatory Arthritis • Lupus • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • CTLA4 • IL10 • IL2 • LAG3 • TCF7