XAV-939 / Novartis - LARVOL DELTA

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

High YEATS2 expression promotes epithelial-mesenchymal transition in gastric cancer cells by activating the Wnt/β-catenin signaling pathway (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "High YEATS2 expression activates Wnt/β-catenin signaling to promote EMT in GC and is correlated with poor prognosis of GC patients."

Journal • Gastric Cancer • Oncology • Solid Tumor • CA 19-9 • CDH1 • CDH2 • VIM

A Novel Mitochondria-Associated Programmed Cell Death-Related Prognostic Model and Validation of Oncogene INHBB in Colorectal Cancer. (PubMed, Int J Genomics) - "IC50 value of some chemotherapeutic agents showed a significant difference between the L- and H-risk groups, containing AZD1332-1463, IGF1R-3801-1738, and XAV939-1268...A prognostic model was constructed based on four key mtPCD-associated genes, namely, ACSL6, INHBB, GPR15, and SRPX. INHBB was upregulated in CRC, and the alleviation of INHBB suppressed the proliferation and migration of CRC cells."

Journal • Colorectal Cancer • Oncology • Solid Tumor • INHBB

Exploring the Impact of 3-O-Methylquercetin on Wnt/β-Catenin Pathway Activity and Its Potential in Neural Processes. (PubMed, Pharmaceuticals (Basel)) - "XAV-939 and PNU-74654 showed inhibitory activity, while BIO, CHIR99021, quercitrin, and 3OMQ enhanced the Wnt/β-catenin pathway... These findings identify 3OMQ as a potent positive modulator of the Wnt/β-catenin pathway, with both in vitro and in vivo neuroprotective effects. Targeting Wnt signaling with compounds such as 3OMQ holds promise for maintaining neuronal health and developing therapeutic strategies for neurodegenerative conditions."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Oncology • WNT3A

FOXJ3 drives mesenchymal stem cell osteogenic differentiation via the Wnt/β‑catenin pathway: A novel regulator implicated in osteoporosis. (PubMed, Mol Med Rep) - "Conversely, the pro‑osteogenic effects of FOXJ3 overexpression were abrogated by the Wnt inhibitor XAV939. These findings establish FOXJ3 as a positive regulator of BMSC osteogenic differentiation acting primarily through the Wnt/β‑catenin pathway, presenting a novel potential therapeutic target for osteoporosis."

Journal • Osteoporosis • Rheumatology • RUNX2

KDM1A Facilitates Oncogenic Potential in Colorectal Cancer Progression Through the Activation of AXIN/GSK3β/β-Catenin Signaling Pathways: Evidence From Integrated Transcriptomics and In Vitro Studies. (PubMed, J Gene Med) - "KDM1A regulates CRC progression by modulating epithelial-mesenchymal transition (EMT), metabolism, and Wnt signaling. Targeting KDM1A with GSK2879552 represents a promising therapeutic strategy for CRC treatment."

Journal • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • AXIN1 • KDM1A

B4galt1 Regulates the WNT-β-Catenin Axis to Control Hematopoietic Stem and Progenitor Cells (HSPCs) Fitness (ASH 2023) - "To confirm the functional significance, we treated B4-/- LSK cells with the Wnt inhibitor XAV939 which normalized cell numbers to control levels and cause a reduction in the observed expansion at the stem and progenitor compartments. These findings suggest that B4galt1 is vital in regulating HSC expansion, likely through the Wnt/β-catenin signaling pathway. Our data provide compelling evidence that B4galt1 regulates steady-state hematopoiesis, through its influence on glycosylation in the bone marrow niche, highlighting the critical role of the B4galt1-Wnt-β-catenin axis in regulating LT-HSC fitness and expansion."

CTNNB1 • FOXM1 • ITGA2B

Akt-Axin1/TNKS-Tiam1-Rac1 mediates insulin-stimulated GLUT4 translocation in skeletal muscle cells. (PubMed, Cell Signal) - "Knockdown of Axin1 inhibited insulin-induced Tiam1 expression, while over-expression of Axin1 and XAV939 had the opposite effect. In summary, our results suggest that an Akt-Axin1/TNKS-Tiam1-Rac1 signaling pathway mediates insulin-stimulated GLUT4 translocation in skeletal muscle cells."

Journal • AXIN1 • IR • PARP1 • RAC1 • SLC2A4 • TIAM1

Retinoic acid-related orphan nuclear receptor alpha inhibits adipogenic differentiation of bone marrow mesenchymal stem cells via activating WNT/β-catenin signaling pathway. (PubMed, Eur J Med Res) - "RORα suppresses adipogenic differentiation of BMSCs, at least in part, by activating WNT/β-catenin signaling."

Journal • FABP4 • LEP • LPL • MYC • PPARG

Oncogenic Role of SAMD4B in Breast Cancer Progression by Activating Wnt/β-Catenin Pathway. (PubMed, Biomolecules) - "Importantly, treatment with XAV-939, a specific Wnt/β-catenin pathway inhibitor, abrogated the pro-oncogenic effects of SAMD4B overexpression, including Wnt/β-catenin pathway activation, enhanced proliferation, and increased metastatic capacity...In summary, our findings clarify that SAMD4B exerts an oncogenic role in breast cancer progression by activating the Wnt/β-catenin pathway. These data identify SAMD4B as a potential therapeutic target in breast cancer, although further in vivo investigations are required to validate its clinical relevance."

Journal • Breast Cancer • Oncology • Solid Tumor • CCND1 • MYC • TP53

Pan-cancer analysis of role of LOXL4 and experiment validation in osteosarcoma. (PubMed, Discov Oncol) - "LOXL4 promotes Osteosarcoma progression via Wnt/β-catenin-mediated EMT and cell proliferation. Its pan-overexpression and associations with the tumor immune microenvironment underscore its potential as a therapeutic target. Targeting LOXL4 or its downstream pathway may offer novel therapeutic strategies for Osteosarcoma."

Journal • Pan tumor • Endometrial Cancer • Melanoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • LOXL4

The Knockdown of ACTL6A Enhances the Radiosensitivity of Esophageal Squamous Cell Carcinoma by Modulating the Wnt/β-Catenin Signaling Pathway. (PubMed, FASEB J) - "Through functional enrichment analysis of gene set enrichment and validation of the mechanism using the Wnt pathway inhibitor XAV939, it was shown that ACTL6A is involved in the regulation of the Wnt/β-catenin signaling pathway. Knockdown of ACTL6A can inhibit the activity of this pathway, thereby increasing the radiosensitivity of esophageal squamous cell carcinoma. ACTL6A may become an important therapeutic target for esophageal squamous cell carcinoma, providing a necessary theoretical basis for future treatment strategies."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Generation of Human Cardiac Organoids from Embryonic Stem Cells via Stepwise Mesoderm Induction and 3D Self-organization. (PubMed, J Vis Exp) - "Mesoderm induction is initiated by treating spheroids for 36-40 h with Activin A (50 ng/mL), bone morphogenetic protein 4 (BMP4, 10 ng/mL), fibroblast growth factor 2 (FGF2, 30 ng/mL), laduviglusib (CHIR99021, 3 µM), and a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002, 5 µM). Cardiac lineage specification is subsequently directed by daily exposure for four days to BMP4 (10 ng/mL), FGF2 (10 ng/mL), a Wnt pathway inhibitor (XAV-939, 5 µM), and retinoic acid (0.5 µM)...Known limitations include the inability to passage organoids and potential central necrosis during extended cultures. In summary, this model provides a scalable and physiologically relevant platform for studying human cardiogenesis, drug responses, and congenital heart diseases."

Journal • Cardiovascular • Heart Failure • BMP4 • CDH5 • FGF2

Stress induces behavioral disorders by promoting microglial phagocytosis via decreasing neuronal Dkk3. (PubMed, Mol Psychiatry) - "Moreover, treatment with a CX3CL1 McAb or XAV-939, an inhibitor of the Wnt pathway, ameliorated CUMS-induced behavioral deficits and decreased microglial phagocytosis of neuronal spines. Taken together, these results demonstrate that Dkk3 plays a critical role in regulating microglial engulfment, an effect which induces long-lasting disruptions of CA1 neurons in response to stress. These findings reveal important new mechanistic insights into the potential for Dkk3 to exert a protective role against MDD pathogenesis."

Journal • Behavior Disorders • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • CX3CL1 • CX3CR1 • DKK3

Notch1 Inhibition Exacerbates APAP-Induced Liver Injury via β-Catenin and Macrophage Polarization. (PubMed, Front Biosci (Landmark Ed)) - "Notch1 inhibition unexpectedly worsens AILI by amplifying macrophage-driven pro-inflammatory responses via β-catenin signaling. These findings highlight the Notch1-β-catenin axis as a key regulator of hepatic macrophage function and a potential therapeutic target for sterile liver inflammation."

Journal • Hepatology • Inflammation • Liver Failure • CTNNB1 • NOTCH1

Dual-edged mechanisms of α-tomatine in hepatocellular carcinoma by suppression of Wnt/β-catenin signaling versus RelB-Driven resistance in tumor therapy. (PubMed, Front Pharmacol) - "Pharmacological interventions using Wnt3a (activation) and XAV939 (inhibition) modulated Wnt/β-catenin signaling, while CRISPR/Cas9-mediated RelB knockout and plasmid-based overexpression established isogenic cell models...This plant-derived alkaloid exerts anti-HCC effects through Wnt pathway modulation, while compensatory RelB activation constrains therapeutic outcomes. Strategic RelB co-targeting establishes a dual pathway phytotherapy paradigm, synergistically merging botanical pharmacodynamics with precision oncology."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • RELB • WNT3A

Acute kidney injury disrupts cardiac remodeling via SerpinA3N. (PubMed, bioRxiv) - "Finally, using H9C2 cells we demonstrated that inhibiting SerpinA3N with XAV939 increased Granzyme B activity. Thus, this study suggests that AKI leads to the development of pro-fibrotic factors in the heart and disrupts cardiac remodeling by SerpinA3N mediated inhibition of serine protease Granzyme B activity. Decreased SerpinA3N expression in the heart followed by AKI could lead to a more balanced extracellular matrix (ECM) composition in the heart with an alleviated pro-fibrotic response."

Journal • Acute Kidney Injury • Cardiovascular • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • GZMB • SERPINA3

The construction of a prognostic nomogram model for colorectal cancer and the prediction of immune characteristics and immune treatment responses based on the bioinformatics analysis of soluble mediator-related genes. (PubMed, Hum Vaccin Immunother) - "Drug sensitivity analysis suggested PF-4708671, PI-103, and XAV939 as potential treatments for HR patients. There was significant correlation between model gene and MMR genes. The CRC prognostic model based on SMRGs effectively predicts patient prognosis and guides treatment strategies."

Journal • Basal Cell Carcinoma • Colorectal Cancer • Non-melanoma Skin Cancer • Oncology • Solid Tumor

GLIS2 Promotes Epithelial-Mesenchymal Transition and Gastric Cancer Progression by Regulating BGN to Activate the Wnt/β-Catenin Pathway. (PubMed, Kaohsiung J Med Sci) - "Functional rescue experiments confirmed that BGN overexpression reverses the inhibitory effects of GLIS2 knockdown, while the Wnt/β-catenin inhibitor XAV-939 effectively blocks BGN's tumor-promoting effects. These findings establish the crucial role of the GLIS2-BGN-Wnt/β-catenin axis in regulating GC EMT and identify novel potential therapeutic targets for GC treatment."

Journal • Gastric Cancer • Oncology • Solid Tumor • BGN • GLIS2

Human myelinated brain organoids with integrated microglia as a model for myelin repair and remyelinating therapies. (PubMed, Sci Transl Med) - "Furthermore, the application of the pro-remyelinating compounds clemastine, XAV939, and BQ3020 further enhanced remyelination in MHBOs +MG but was ineffective in the absence of microglia. Cross-validation of our findings in mouse cerebellar slice cultures confirmed that the pro-remyelinating compounds were effective ex vivo, suggesting the translational potential of our MHBOs +MG model."

Journal • CNS Disorders • Multiple Sclerosis

Notoginsenoside R1 Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Apoptosis via Activating Wnt/β-Catenin Signaling. (PubMed, Am J Chin Med) - "Experimentally, the protective effects of NGR1 in inhibiting cardiomyocyte apoptosis, improving cardiac function, and reducing infarct size were significantly attenuated with the use of the Wnt signaling inhibitor XAV-939. Collectively, our investigation demonstrated that NGR1 improves myocardial injury triggered by ischemia/reperfusion (I/R) by enhancing Wnt/[Formula: see text]-catenin pathway activity, which in turn suppresses apoptosis."

Journal • Cardiovascular • Myocardial Ischemia • Reperfusion Injury

SALL2-Mediated Suppression of WNT Signaling Through Transcriptional Control of AXIN2 in Colorectal Cancer Cells. (PubMed, Int J Mol Sci) - "Furthermore, SALL2 expression potentiated the pro-apoptotic effects of the Wnt pathway inhibitor XAV939 in CRC cells, suggesting a role in sensitizing cells to Wnt-targeted therapies. Collectively, these findings identify SALL2 as a negative regulator of Wnt/β-catenin signaling and support its potential as a prognostic biomarker and therapeutic target in colorectal cancer."

Journal • Colorectal Cancer • Oncology • Solid Tumor

Dujieqing decoction suppresses multiple myeloma growth by inhibiting the Wnt/β-catenin pathway. (PubMed, J Tradit Chin Med) - "Our results indicate that the DJQ decoction suppresses tumor progression by inhibiting the Wnt/β-catenin pathway, offering a promising treatment approach for MM."

Journal • Genetic Disorders • Hematological Malignancies • Immunology • Multiple Myeloma • Obesity • Oncology • Primary Immunodeficiency • CCND1 • MYC

Phillygenin Improves the Focal Adhesion Kinase/Glycogen Synthase Kinase 3β/β-Catenin Axis to Promote Mesenchymal Stem Cell Osteogenic Differentiation. (PubMed, Phytother Res) - "Inhibition of the pathway, achieved through the use of Y15 and XAV-939, attenuated PHI-induced osteogenesis. These findings indicate that PHI enhances BMSCs osteogenesis via the FAK/GSK-3β/β-catenin axis, thereby restoring bone metabolic balance. The results highlight PHI's dual regulatory potential in the management of bone disorders, particularly, estrogen deficiency-related osteoporosis, and suggest its potential applications in the therapeutic intervention of bone diseases."

Journal • Orthopedics • Osteoporosis • Rheumatology • CTNNB1 • GSK3B • RUNX2 • SPP1

Progesterone Upregulated the Expression of AQP1 and AQP5 in the Mice Uterine Myometrium to Delay Preterm Birth via β-Catenin Signaling Pathway. (PubMed, FASEB J) - "Inhibiting β-Catenin with XAV939 eliminated these alterations. Progesterone could prevent PTB in pregnant mice, possibly through upregulating myometrium AQP1, AQP5 expression via activating the activity of β-Catenin."

Journal • Preclinical • AQP1 • MT-CO2