XAV-939 / Novartis - LARVOL DELTA

Imiquimod targets tankyrase 2 to suppress wnt-active colorectal cancer (AACR 2026) - "XAV939, a small-molecule inhibitor of TNKS, has been widely used to study Wnt pathway inhibition. This study reveals a novel potential route for repurposing a clinically approved agent to suppress Wnt-driven oncogenesis. This is the first study to propose a mechanism by which IMQ may inhibit Wnt/β-catenin signaling."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • AXIN1 • PARP1 • TNKS2

Mechanism of KLF4 Inhibition of epithelial-mesenchymal transition in gastric cancer cells. (PubMed, Open Life Sci) - "Following transfection, the Wnt signaling pathway inhibitor XAV-939 and agonist SKL2001 were administered to the KLF4-overexpressing cells...Results demonstrated that KLF4 overexpression inhibits EMT in gastric cancer cells through the Wnt/β-catenin signaling pathway. Thus, this study concludes that KLF4 may modulate EMT in gastric cancer cells via the Wnt/β-catenin pathway."

Journal • Gastric Cancer • Oncology • Solid Tumor • KLF4

MAGI3 deficiency unleashes β-catenin conformational change to drive metastatic progression and mTOR inhibitor resistance in ccRCC. (PubMed, Cell Death Dis) - "Combining Everolimus with the Wnt inhibitor XAV-939 slashed viability and invasion in resistant cells. Its loss defines a metastatic, therapy-resistant subtype targetable by dual mTOR/Wnt blockade. Therefore, MAGI3 expression may stratify patients for personalized therapy."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CTNNB1

Cassia polysaccharides can regulate the effect of low PAX6 expression on the function of ARPE-19 cells through the Wnt/β-catenin pathway. (PubMed, Mol Vis) - "The ARPE-19 cell line with diminished PAX6 expression was established using a lentiviral approach and the addition of XAV-939, an inhibitor of Wnt/β-catenin...Scratch assay results demonstrated slower wound healing in PAX6-shRNA compared to controls over 72 h, with no significant differences observed in the cassia polysaccharides. Cassia polysaccharides may mitigate ARPE-19 cell damage induced by low PAX6 expression through modulation of Wnt/β-catenin, potentially slowing the progression of myopia and offering a protective effect on vision."

Journal • Infectious Disease • Ophthalmology • CDK1 • COL1A1 • CTNNB1 • MMP2 • PAX6 • PCNA • TGFB1 • WNT2

IFIT3-DVL interaction promotes malignant progression of lung squamous cell carcinoma and large-cell lung carcinoma via canonical WNT signaling. (PubMed, J Biol Chem) - "DVL2 knockdown or XAV-939 significantly abrogates above effects mediated by IFIT3 (p <0.05). Overall, we demonstrated a novel signal transduction pathway where IFIT3 interacts with DVL2 to stabilize cytosolic β-catenin and promote β-catenin nuclear translocation via DVL2 phosphorylation, enhancing canonical WNT signaling activity and providing a potential target for clinical intervention in LUSC and LCLC."

Journal • Large Cell Carcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CCND1 • CDC42 • CDK4 • DVL1 • MMP2 • MYC

AXIN1-Dependent Regulation of Lung Macrophage MHC II Expression Shapes CD4⁺ T Cell Responses during BCG Infection. (PubMed, Biochem Cell Biol) - "In Tcf/Lef-Gfp transgenic mice intratracheally infected with Mycobacterium bovis BCG, treatment with XAV939 to upregulate AXIN1 expression inhibited Wnt/β-catenin signaling, reduced the proportions of CD4 + T cells and macrophages, and decreased the percentage of MHC-II-positive macrophages...The accumulated evidence indicates that AXIN1 plays a critical function within modulating macrophage phagocytosis and CD4 + T cell reactions because of M. tb infection. Understanding the mechanisms underlying the regulation of the innate-to-adaptive immune transition by AXIN1 could provide new insights into TB pathogenesis and inform the development of novel therapeutic and vaccine strategies."

Journal • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • AXIN1 • CD4

Exploring the microbial metabolomes for Wnt pathway modulators: a multi-scale computational pipeline targeting Tankyrase in colorectal cancer. (PubMed, In Silico Pharmacol) - "Although XAV939 is a known TNKS-1 inhibitor, it demonstrated comparatively reduced efficacy across binding and stability metrics. In conclusion, this integrative computational evidence supports microbial-derived compounds as promising natural candidates for TNKS-1 inhibition, offering a new avenue for in vivo validation and structure-guided discovery of next-generation microbe-based therapeutics for colorectal cancer. The online version contains supplementary material available at 10.1007/s40203-026-00585-9."

Journal • Colorectal Cancer • Oncology • Solid Tumor • AXIN1 • PARP1 • TNKS2

Wnt/β-Catenin Activation by iCRT3 Enhanced the Pluripotency of Bovine Expanded Pluripotent Stem Cells. (PubMed, Animals (Basel)) - "Here we systematically investigated the role of Wnt/β-catenin signaling and its key effector TCF1 in bovine expanded pluripotent stem cells (bEPSCs) using a combination of small molecules (CHIR99021, XAV939, IWR-1, iCRT3)...Transcriptome profiling also demonstrated that this combination drives bEPSCs toward a hybrid naïve/formative pluripotency state. Together, these results demonstrate that Wnt/β-catenin signaling homeostasis is critical for bovine pluripotency regulation, which provides a foundation for refining livestock stem cell culture conditions and understanding the evolution of pluripotency networks."

Journal • POU5F1 • SOX2 • TCF3

microRNA-544a-3p as a new modulator of the Wnt-signalling network in the articular cartilage and osteoarthritis. (PubMed, Osteoarthritis Cartilage) - "Our results point to miR-544a-3p as a new, important modulator of the Wnt signalling network within the articular cartilage suggesting a key role for microRNAs in regulating how the multiple branches of the network and their interaction modulate cartilage homeostasis."

Journal • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology • ACAN • MMP13

Therapeutic effects of human amniotic mesenchymal stem cell-derived exosomes on stem cell proliferation in irradiated salivary glands via the Wnt pathway. (PubMed, Open Life Sci) - "In contrast, administration of XAV-939 alone was associated with reduced proliferation and diminished stem cell marker expression. These findings suggest that hAMSC-derived exosomes promote stem cell proliferation and structural restoration in irradiated salivary gland tissue, potentially through activation of the Wnt signaling pathway."

Journal

Oral Streptococcus salivarius Couples Neutrophil IRGM1 Signaling to NET Formation and Colorectal Cancer Metastasis. (PubMed, Adv Sci (Weinh)) - "Functional validation experiments show that conditional deletion of IRGM1 or pharmacological inhibition of downstream signaling using XAV-939 markedly attenuates S. salivarius-induced NET formation, indicating the requirement of this pathway in the metastatic process. Furthermore, clinical sample analyses reveal that S. salivarius is significantly enriched in the tongue coating and feces of patients with CRC and is elevated within the tumor microenvironment. Together, these findings identify IRGM1-IQGAP1-mediated Wnt5a-PI3K/AKT signaling as a mechanistic link between oral microbiota and neutrophil-driven immune responses in cancer metastasis."

Journal • Colorectal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • IQGAP1

β-Catenin-Facilitated Glycolytic Reprogramming Fuels TNBC Progression: Therapeutic Blockade with XAV939. (PubMed, Technol Cancer Res Treat) - "In vitro, XAV939 suppressed β-catenin-driven aerobic glycolysis in TNBC cells, downregulating β-catenin and glycolytic proteins, reducing glycolytic activity, and impairing aggressive phenotypes (proliferation, migration, invasion, clonogenicity).ConclusionOverall, our results highlight the crucial role of β-catenin in controlling aerobic glycolysis via regulation of key glycolytic proteins, thereby positively driving the progression and metastasis of TNBCs. Additionally, our data strongly establish that XAV939 effectively inhibits glycolytic phenotype, thereby suggesting its therapeutic potential in TNBC patients."

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

Wnt-dependent modulation of alveolar epithelial phenotypes and barrier function in human progenitor-like cells. (PubMed, Biochem Biophys Res Commun) - "Within ALI, β-catenin inhibition by XAV939 elevated AT1 features while retaining AT2 protein expression, but was accompanied by reduced AT2 marker expression at the transcriptional level compared with the YAC(-) condition...Collectively, these findings demonstrate that β-catenin modulation within ALI biases the alveolar epithelial profile toward AT1-like features, whereas the YAC(-) condition sustains a balanced AT1/AT2 state with superior epithelial barrier performance and repair capacity. This platform provides a single-monolayer system suitable for dissecting alveolar epithelial differentiation and functional maintenance."

Journal • CTNNB1 • PDPN • SFTPC • SFTPD

Evaluation of ELU42 Topical Spray for the Treatment of Diabetic Foot Ulcers (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: Eluciderm Inc

New P1/2 trial

EVADR lncRNA Mitigates Neonatal Hypoxic-Ischemic Brain Injury via the miR-145→WNT/β-Catenin Axis and Exhibits Biomarker Potential. (PubMed, Neurochem Res) - "Genetic (si-CTNNB1/si-WNT3A) and pharmacologic (XAV939/CHIR99021) cross-validation demonstrated pathway necessity and rescue...Circulating EVADR levels in plasma/CSF correlated with injury severity; ROC analyses indicated diagnostic potential alone and combined with S100B/NSE. These data support EVADR-miR-145→WNT/β-catenin as a mechanistic axis with translational relevance."

Biomarker • Journal • Cardiovascular • CNS Disorders • Inflammation • Vascular Neurology • CTNNB1 • HIF1A • MIR145 • S100B • WNT3A

TRPA1 mediates ozone-induced murine model of COPD through the Wnt5a/GSK-3β/β-catenin pathway. (PubMed, Environ Pollut) - "C57BL/6J or TRPA1-deficient mice underwent ozone exposure (2.5 ppm, 3 h/session) every 3 days for 2 months, following administration of either the TRPA1 antagonist A967079 or the Wnt5a/GSK3β/β-catenin inhibitor XAV-939. Therapeutic targeting of both TRPA1 and Wnt5a/GSK3β/β-catenin pathway may represent a promising intervention strategy for ozone-associated COPD pathogenesis. This study elucidates the mechanisms through which ambient O3 impairs respiratory health across the general population."

Journal • Preclinical • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • TRPA1

Hedgehog-Wnt Crosstalk Orchestrates Submandibular Gland Morphogenesis in Mice. (PubMed, Genesis) - "Critically, the co-administration of the Wnt inhibitor XAV939 with vismodegib in ex vivo cultures partially rescued the branching defects caused by Hh inhibition. We conclude that Hh signaling promotes murine SMG morphogenesis, at least in part, by tonically inhibiting the Wnt pathway. This study unveils a novel inhibitory crosstalk between Hh and Wnt signaling that is essential for normal salivary gland development."

Journal • Preclinical • GLI1 • PTCH1

Melatonin Suppresses Cellular Senescence in Diabetic kidney disease though the Wnt/β-catenin signaling pathway. (PubMed, Eur J Pharmacol) - "Mechanistically, melatonin potently inhibited the upregulation of key proteins in the Wnt/β-catenin signaling pathway, including Wnt3a, β-catenin, p-GSK-3β, c-Myc, and Cyclin-D1, with an efficacy comparable to that of the Wnt inhibitor XAV-939. Notably, experiments in HK-2 cells further demonstrated that treatment with the Wnt/β-catenin activator BML-284 abrogated the protective effects of melatonin. Overall, these findings demonstrate that melatonin suppresses cellular senescence in DKD by inhibiting the Wnt/β-catenin pathway."

Journal • Diabetes • Diabetic Nephropathy • Nephrology • Renal Disease • CCND1 • CDKN1A • CDKN2A • MYC • WNT3A

ZNF710 regulates the proliferation, migration, apoptosis, and cell cycle progression of gastric cancer cells through the Wnt/β-catenin pathway. (PubMed, Am J Cancer Res) - "ZNF710 is highly expressed in GC and promotes GC cell proliferation, migration, and invasion while inhibiting apoptosis by activating the Wnt/β-catenin pathway, suggesting it may serve as a potential therapeutic target for GC."

Journal • Gastric Cancer • Oncology • Solid Tumor

CBX4 Drives Gastric Cancer Progression by Activating β-Catenin Signaling. (PubMed, Oncol Res) - "The functional dependency on Wnt/β-catenin signaling was tested using the pharmacological inhibitor XAV939 in CBX4-overexpressing cells...CBX4 upregulation promotes GC progression via β-catenin signaling activation. The CBX4/β-catenin axis emerges as a promising therapeutic target, offering potential for the development of precision treatment strategies in GC management."

Journal • Gastric Cancer • Oncology • Solid Tumor

Pin1 as a Central Modulator of Wnt/β-Catenin Signaling in Pulmonary Fibrosis: Interplay with EBV-LMP1 and Therapeutic Implications. (PubMed, Iran J Pharm Res) - "Treatment with Wnt3a further enhanced β-catenin expression by 2.4-fold, while XAV939 reduced it by 66% (P < 0.01)...Pin1 inhibitors effectively downregulate this signaling cascade, even under hyperactive conditions, highlighting their therapeutic potential for PF treatment. While Pin1 inhibitors effectively downregulate this signaling cascade even under hyperactive conditions, their therapeutic potential remains to be validated in preclinical models."

Journal • Epstein-Barr Virus Infections • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • AXIN2 • CCND1 • PIN1 • WNT3A

Pan-cancer multi-omics reveals DCAF7 as an immune-modulating prognostic driver and Wnt/β-catenin activator in hepatocellular carcinoma. (PubMed, Clin Transl Med) - "DCAF7 is up-regulated in various tumours and correlates with poor prognosis, particularly in LIHC. High DCAF7 expression is linked to CD4+ T cell infiltration, up-regulation of immune checkpoint genes and increased tumour mutational burden, suggesting a role in tumour immune escape. DCAF7 stabilises β-catenin by enhancing GSK-3β Ser9 phosphorylation, thereby driving c-Myc/cyclin D1 expression and contributing to proliferation and migration in LIHC. DCAF7-high tumours demonstrate therapeutic vulnerability to 17-AAG, docetaxel and CDK/GSK-3 inhibitor, revealing potential targeted treatment strategies."

IO biomarker • Journal • Pan tumor • Tumor mutational burden • Hepatocellular Cancer • Microsatellite Instability • Oncology • Solid Tumor • Targeted Protein Degradation • CCND1 • CD4 • DDB1 • MSI • MYC • PD-1 • PD-L1 • TIGIT • TMB

Characterization of Differential GPX4 Essentiality Between Intrahepatic and Extrahepatic Cholangiocarcinoma via Leveraging of a Large-Scale Functional Genomic Screen. (PubMed, Int J Mol Sci) - "Co-treatment with the tankyrase inhibitor XAV-939 and RSL3 enhanced growth inhibition of eCCA cells, indicating that WNT signaling contributed to ferroptosis resistance. These findings indicate that iCCA exhibits a preferential dependency on GPX4, whereas WNT-β-catenin signaling mediates resistance in eCCA. Collectively, the results clarify the molecular basis of subtype-specific ferroptosis vulnerability and offer a rationale for combinatorial therapeutic strategies that integrate GPX4 and WNT pathway inhibition when treating refractory eCCA."

Journal • Biliary Cancer • Cholangiocarcinoma • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Oncology • Solid Tumor • GPX4

Overexpression of the lncRNA TUG1 regulates high-glucose-induced endocytic clearance dysfunction in HLSECs via the Wnt/β-catenin signaling pathway. (PubMed, Eur J Med Res) - "LncRNA TUG1 attenuates high glucose-induced endocytic clearance dysfunction in HLSECs, potentially via regulating the Wnt/β-catenin pathway. As a key regulatory target for HLSEC endocytic function, TUG1 offers novel perspectives for understanding MAFLD's pathogenesis and developing targeted therapies."

Journal • Diabetes • Dyslipidemia • Hepatology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus • CAV1 • CCND1 • TUG1

Canonical Wnt signaling affects calcium homeostasis in serum-treated AC16 cells through MLN-mediated SERCA2a regulation. (PubMed, J Mol Cell Biol) - "While Wnt activation elevates cytosol calcium in serum-free conditions, FBS supplementation reverses this response: Wnt inhibitors (SFRP2, XAV939, and LF3) induce cytosol calcium accumulation, while the activators (LiCl and Wnt3a) lose efficacy...Our work establishes a serum-dependent regulatory axis where Wnt/β-catenin signaling maintains calcium homeostasis by repressing MLN, thereby preserving SERCA2a function. This FBS-induced shift mirrors pathological adaptations in heart failure, positioning MLN as a therapeutic target for calcium-handling disorders."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • RYR2 • SFRP2 • WNT3A