XAV-939 / Novartis - LARVOL DELTA

WWOX Suppresses Gastric Cancer Cell Proliferation, Migration, and EMT by Negatively Regulating the Wnt/β-Catenin Signaling Pathway. (PubMed, Ann Clin Lab Sci) - "WWOX suppresses GC cell proliferation, invasion, and EMT both in vitro and in vivo by negatively regulating the Wnt/β-catenin signaling pathway. These findings provide a mechanistic basis for targeting the WWOX/Wnt/β-catenin axis as a potential therapeutic strategy for GC."

Journal • Gastric Cancer • Oncology • Solid Tumor • WWOX

DNA Polymerase θ Drives Colorectal Cancer Progression through Wnt/β-Catenin Activation and Shows Potential Association with Immunosuppressive Microenvironment Remodeling. (PubMed, Oncol Res) - "The Wnt inhibitor XAV939 reversed the POLQ overexpression-induced malignant phenotype, while the Wnt activator SKL2001 partially rescued the knockdown phenotype...Bioinformatic inference suggests a potential association with an immunosuppressive microenvironment, but this finding remains correlative and requires experimental confirmation. These findings suggest that POLQ is a potential prognostic biomarker and therapeutic target, though further validation in prospective, multicenter cohorts is warranted."

Journal • Colorectal Cancer • Oncology • Solid Tumor • Thrombosis • POLQ

Targeting the CRYAB/β-Catenin Axis with an MMP-9-Responsive Hydrogel Disrupts CTC Clusters to Suppress Progression of Hepatocellular Carcinoma after Radiofrequency Ablation. (PubMed, Adv Sci (Weinh)) - "To suppress this pathological cascade, we engineered a matrix metalloproteinase-9 (MMP-9)-responsive thermosensitive hydrogel system (XB@Gel) that enables localized and sustained co-delivery of the β-catenin inhibitor XAV-939 and the PD-L1 inhibitor BMS-202. XB@Gel effectively reverses EMT, reprograms the immunosuppressive microenvironment, reduces CTC clusters, and robustly inhibits HCC recurrence and metastasis after iRFA. Collectively, our findings identify the CRYAB/β-catenin axis as a key transducer of thermal stress into a pro-metastatic signaling cascade in residual HCC and establish XB@Gel as a promising multi-dimensional therapeutic strategy to combat post-iRFA progression."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • CRYAB • CTNNB1 • MMP9

Indole-3-carboxylic acid promotes senescence of colorectal cancer cells by inhibiting the binding of Netrin-1 to UNC5B. (PubMed, Cell Signal) - "I3C promotes CRC cellular senescence and suppresses tumor progression by blocking Netrin-1/UNC5B binding, likely through modulating Wnt/β-catenin pathway. This reveals a novel anticancer mechanism of I3C and a potential CRC therapeutic target."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CCND1 • MYC • NTN1

Biomimetic Brain-Targeted Delivery of Esterified XAV939 for Treating Autism-Associated Social Deficits. (PubMed, Pharmaceutics) - "At a half-dose of XAV939-L1, XAV939-L1-BT exhibited significant social improvement effects without obvious hepatic and intestinal toxicity. Our data demonstrated an esterified XAV939 and its biomimetic brain-targeted formula as a potential drug candidate for treating ASD-associated social dysfunction."

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

Dlc1 deletion activates the canonical Wnt pathway at an early stage and affects subsequent cardiac differentiation in mouse embryonic stem cells. (PubMed, Genes Dis) - "These results were confirmed by rescue experiments with the Wnt pathway inhibitor XAV-939. Furthermore, we found that the Dlc1 knockout activated canonical Wnt signaling by affecting the degradation and nuclear transportation of β-catenin. In conclusion, Dlc1 is involved in regulating embryonic stem cell cardiac differentiation by affecting canonical Wnt signaling at an early stage."

Journal • Preclinical • Liver Cancer • Oncology • Solid Tumor • CTNNB1

Fgfr3-Wnt signaling crosstalk is involved in maintaining cranial suture integrity. (PubMed, Bone Res) - "Pharmacological inhibition of canonical Wnt signaling during suture development using the β-catenin inhibitor XAV939 restored fgf18 expression, partially normalized levels of the BMP antagonist grem1, reduced SMAD1/5 phosphorylation, and produced a significant improvement in cranial suture morphology. In conclusion, these findings position Fgfr3 as a central regulator of cranial suture formation and homeostasis, acting through intricate cross-talk between the FGF, canonical Wnt, and possibly BMP signaling pathways. These data offer new insights into the biology of cranial suture and FGFR3-related craniosynostoses."

Journal • CTNNB1 • FGF18 • FGFR3

A preliminary exploration of the role and mechanisms of CD93 in promoting the malignant progression of head and neck squamous cell carcinoma. (PubMed, Front Pharmacol) - "CD93 expression was associated with Wnt/β-catenin activation; CHIR99021 reversed the effects of CD93 knockdown, whereas XAV939 attenuated changes induced by CD93 overexpression...Clodronate liposome-mediated macrophage depletion reduced HSC3-shNC tumor growth and narrowed the difference between HSC3-shNC and HSC3-shCD93 tumors...Docking analysis provides a preliminary structural hypothesis for a potential CD93-LRP6 E1E2 spatial association. CD93 may represent a prognostic biomarker and candidate therapeutic target in HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD93 • MRC1

Unveiling isoleucyl-tRNA synthetase 2 as a novel driver of breast cancer via β-catenin pathway activation. (PubMed, J Cell Commun Signal) - "Notably, the β-catenin inhibitor XAV-939 reversed IARS2-driven breast cancer malignant progression...Overall, our findings uncovered that silencing IARS2 blocked the β-catenin signaling axis, thereby impeding breast cancer progression. IARS2 might become a promising novel therapeutic target for breast cancer intervention."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • LARS2

TRIM9 regulates the proliferation and apoptosis of dermal papilla cells by activating the Wnt/β-catenin signaling pathway to improve androgenetic alopecia. (PubMed, Pathol Res Pract) - "TRIM9 competitively binds to β-TrCP, inhibiting β-TrCP-mediated ubiquitination and degradation of β-catenin, activating the Wnt/β-catenin signaling pathway, promoting hDPCs proliferation, suppressing apoptosis, and ultimately ameliorating AGA progression."

Journal • Alopecia • Immunology • Targeted Protein Degradation • TRIM9

Exogenous recombinant complement proteins C3a and C5a regulate osteogenic differentiation of P-PDLSCs: a process associated with the Wnt/beta-catenin axis. (PubMed, Immunobiology) - "Exogenous recombinant C3a/C5a is associated with increased early osteogenic differentiation of P-PDLSCs, a process correlated with the activation of the Wnt/β-catenin signaling pathway, providing potential insights into regenerative strategies for periodontal tissues."

Journal • CTNNB1 • IL1B • RUNX2 • TNFA

Tankyrase inhibition restores chemosensitivity in triple-negative breast cancer cells by disrupting TFEB/β-Catenin/ABCG2 axis. (PubMed, Mol Biol Rep) - "Targeting TNKS represents a potentially effective therapeutic approach to address cisplatin resistance and improve treatment outcomes in TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ABCG2 • CTNNB1 • TFEB

Autologous platelet-rich gel promotes diabetic foot ulcer wound healing by activating the Wnt/β-catenin signaling pathway. (PubMed, Connect Tissue Res) - "Importantly, the beneficial effects of APG on wound healing, tissue repair, and collagen deposition were effectively abolished by co-treatment with XAV-939. These findings reveal a novel mechanism underlying APG-mediated DFU healing and provide a theoretical foundation for the beneficial role of Wnt/β-catenin signaling in wound repair. This study offers new perspectives and directions for ulcer treatment strategies."

Journal • Diabetes • Metabolic Disorders • STAT3

Wnt/Chemerin Signaling Involved in Exercise Training Preventing Diaphragm Dysfunction Induced by Cigarette Smoke. (PubMed, Biomedicines) - "Combined XAV939 and exercise training significantly decreased chemerin protein level (p < 0.01). Exercise training can downregulate inflammation levels and improve diaphragm dysfunction in CS-exposed mice, partially by enhancing Wnt expression and reducing abnormally activated chemerin."

Journal • Inflammation • Targeted Protein Degradation • CTNNB1 • IL1B

Morroniside alleviates CoCrMo particle-induced osteogenic impairment by activating Wnt/β-catenin signalling. (PubMed, Cell Signal) - "Notably, inhibiting the Wnt signalling pathway with XAV939 abolished the protective effects of Mor in both models. These findings indicate that Mor alleviates CoP-induced osteolysis by restoring osteogenic function via the Wnt/β-catenin pathway, highlighting its potential as a therapeutic agent for PPO."

Journal • Orthopedics • Osteoporosis • Rheumatology

M2 microglial exosomal miR-1949 ameliorates sepsis-associated encephalopathy through DKK1/Wnt/β-catenin-mediated microglial repolarization. (PubMed, Arch Pharm Res) - "What's more, the effects of M2-EXO-miR-1949 mimic were reversed by the Wnt/β-catenin pathway inhibitor XAV939...In summary, the present study indicates that M2-EXO, especially its contained miR-1949, ameliorates LPS-induced SAE in mice through inhibiting DKK1 to activate the Wnt/β-catenin pathway, thereby leading to microglial phenotypic transformation and neuroinflammation inhibition. This study reveals a novel mechanism by which M2-EXO and miRNA ameliorate SAE, providing a theoretical basis for further studies."

Journal • CNS Disorders • Infectious Disease • Inflammation • Septic Shock • CTNNB1 • DKK1 • MIR194

Serine Protease Inhibitor, SerpinA3N, Disrupts Cardiac Remodeling After Acute Kidney Injury (ATC 2026) - "These findings identify SerpinA3N as a key mediator of CRS-3, linking renal injury to maladaptive cardiac remodeling through the inhibition of Granzyme B. Reducing SerpinA3N levels with inhibitors in the heart before kidney transplantation may rebalance extracellular matrix turnover and mitigate post-AKI cardiac fibrosis."

Acute Kidney Injury • Cardiovascular • Fibrosis • Immunology • Metabolic Disorders • Nephrology • Renal Disease • Reperfusion Injury • COL1A1 • FN1 • GZMB • SERPINA3 • TGFB1

Dual PARP/Tankyrase Inhibition Enhances Antitumor Efficacy in PTEN-Deficient Endometrial Cancer. (PubMed, J Cell Mol Med) - "In vitro, JPI-547 and olaparib more effectively reduced cell survival in PTEN-deficient cells, and combined treatment with olaparib and the TNKS inhibitor XAV-939 induced synergistic cytotoxicity with elevated DNA double-strand breaks. PTEN knockdown further showed enhanced vulnerability to combined targeting. These findings show that JPI-547 enhances antitumor efficacy in PTEN-deficient EC by disrupting DNA repair pathways and Wnt signalling, supporting dual PARP/TNKS inhibition as a potential therapeutic strategy and providing a rationale for further clinical evaluation."

Journal • Endometrial Cancer • Oncology • Solid Tumor • BRCA • PTEN • RAD51

KIF11 drives ovarian cancer progression and cisplatin resistance via the Wnt/β-catenin signaling pathway. (PubMed, Biochem Biophys Res Commun) - "KIF11 can promote the malignant phenotype and DDP resistance of tumor cells by activating the Wnt/β-catenin signaling pathway in OC. Therefore, KIF11 has the potential to serve as a biomarker for predicting OC progression and the efficacy of DDP treatment."

Journal • Oncology • Ovarian Cancer • Solid Tumor • BUB1B • CCNB1 • KIF11 • KIF23

Retinoic Acid-Related Orphan Nuclear Receptor Alpha Promotes Cartilage Degeneration in Osteoarthritis by Activating the Wnt/β-Catenin Pathway. (PubMed, FASEB J) - "Notably, the Wnt/β-catenin pathway inhibitor XAV-939 ameliorated RORα-induced ECM degradation in chondrocytes...Notably, the Wnt/β-catenin signaling pathway plays a critical role in RORα-mediated regulation of ECM degradation in chondrocytes. In summary, the RORα-Wnt/β-catenin pathway axis is pivotal in the pathogenesis of OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • COL2A1

PDRG1 induced by SP1 facilitates the proliferation and metastasis of hepatocellular carcinoma by activating the Wnt/β-catenin pathway. (PubMed, MedScience) - "Mechanistically, PDRG1 activated Wnt/β-catenin signaling, elevating levels of β-catenin, c-Myc, and phosphorylated GSK-3β, and the oncogenic effects of PDRG1 were reversed by the Wnt pathway inhibitor XAV939...The pro-tumor effects of SP1 were rescued by PDRG1 silencing, indicating that SP1 acts through PDRG1. Collectively, our study identifies SP1 as an upstream transcriptional activator of PDRG1 and defines the SP1/PDRG1/Wnt/β-catenin axis as a key regulatory pathway promoting HCC progression, suggesting its potential as a prognostic biomarker and therapeutic target."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • MYC

Glutamine deprivation enhances doxorubicin sensitivity in osteosarcoma by downregulating GLUD1 and promoting ROS-mediated inhibition of Wnt/β-catenin signaling. (PubMed, Pathol Res Pract) - "In vivo, the combination of L-asparaginase and doxorubicin, as well as treatment with XAV-939, significantly inhibited tumor growth, whereas NAC attenuated these effects. In conclusion, glutamine deprivation enhances doxorubicin sensitivity in osteosarcoma. Mechanistically, this chemosensitizing effect is mediated by downregulation of GLUD1, which promotes intracellular ROS accumulation and subsequently suppresses Wnt/β-catenin signaling."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CASP3 • GLUD1

Syndecan-4 in microglia mediates ischemic stroke-induced mitochondrial dysfunction and blood-brain barrier damage by interacting with Dishevelled. (PubMed, Sci Rep) - "XAV-939 reversed the protective effects of SDC4 interference. Mechanistically, SDC4 interacts with Dishevelled (Dvl) in microglia, physically sequestering Dvl and inhibiting Wnt/β-catenin signaling, ultimately leading to microglial mitochondrial dysfunction and associated BBB damage. The interaction between SDC4 and Dvl promotes mitochondrial dysfunction in microglia and is closely associated with the disruption of BBB integrity, thus offering a potential therapeutic strategy for the clinical treatment of cerebral ischemia."

Journal • Cardiovascular • Ischemic stroke • Metabolic Disorders • Reperfusion Injury • CLDN5 • OCLN • SDC4

Pyraclostrobin triggers pulmonary inflammation, oxidative stress, and fibrosis in mouse via Wnt/β-catenin signaling. (PubMed, Chem Biol Interact) - "Inhibition of the Wnt/β-catenin pathway with XAV-939 mitigated inflammation, oxidative stress, and fibrosis. These results indicate that the Wnt/β-catenin pathway integrates inflammatory and oxidative responses to promote PYR-induced pulmonary fibrosis, suggesting a potential therapeutic target for mitigating fungicide-related lung damage."

Journal • Preclinical • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL10 • IL1B • IL6 • TGFB1 • TNFA

Tempol Protects Against Radiation Injury in the Submandibular Gland Through the β-Catenin Signaling Pathway. (PubMed, J Oral Pathol Med) - "TPL exerted protective effects against IR-induced damage in Hs917.T cells and the SMG of C57BL/6 mice through activating the β-catenin signaling pathway, inhibiting cell apoptosis, and alleviating oxidative stress."

IO biomarker • Journal • BCL2 • CASP9