Undisclosed YAP/TAZ-TEAD inhibitor / Hanmi - LARVOL DELTA

The cardiac glycoside periplocymarin sensitizes gastric cancer to ferroptosis via the ATP1A1-Src-YAP/TAZ-TFRC axis. (PubMed, Phytomedicine) - "Our findings establish the cardiac glycoside PPM as a novel ferroptosis sensitizer that targets ATP1A1 to activate the Src-YAP/TAZ-TFRC axis, providing mechanistic insights for repurposing cardiac glycosides as ferroptosis modulators in precision combinatorial cancer therapy."

Journal • Cardiovascular • Gastric Cancer • Oncology • Solid Tumor • ATP1A1

TEAD inhibition as a therapeutic strategy for diffuse-type gastric cancer (AACR 2025) - "Therefore, we evaluated the activity and mechanism of TEAD inhibitors in DGC preclinical models. Gastric cancer patient-derived organoids (PDOs) and cell lines were treated with TEAD inhibitors (VT103, VT107) and/or 5-fluorouracil (5-FU) for in vitro assays evaluating cell proliferation or invasion. The YAP/TAZ-TEAD pathway is an important driver of gastric cancer growth and metastasis, particularly in DGC where it may promote EMT. TEAD inhibition reduces gastric cancer growth and invasion in vitro and in vivo in preclinical models and demonstrates synergistic activity with 5-FU chemotherapy. These results suggest a potential role for further investigation of clinical efficacy of TEAD inhibitors in patients with DGC."

Gastric Cancer • Oncology • Solid Tumor • CASP3 • CDH1 • KRAS • SNAI2 • TEAD1 • TP53 • YAP1

Moxidectin unravels the role of Hippo-YAP pathway in maintaining immunity of glioblastoma multiforme. (PubMed, Mol Cancer Ther) - "Inhibition of MEK-ERK by moxidectin ultimately led to blockade of the nuclear translocation and transcriptional activity of YAP/TAZ-TEAD complex in various GBM cells. Chronic moxidectin treatment did not cause any toxicity in mice based on our toxicological evaluation. Moxidectin is an FDA approved drug, findings from our study will promote its clinical investigation as a potential therapeutic agent for GBM patients."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

High dose methylprednisolone mediates YAP/TAZ-TEAD in vocal fold fibroblasts with macrophages. (PubMed, Sci Rep) - "The pro-fibrotic effects of glucocorticoids may lead to a suboptimal therapeutic response for vocal fold (VF) pathology. Verteporfin attenuated upregulation of CCN2, but not PTGS2 downregulation. High concentration methylprednisolone induced nuclear localization of S211-pGR and upregulated fibrotic genes mediated by YAP/TAZ activation."

Journal • Fibrosis • Immunology • Inflammation • Otorhinolaryngology • ACTA2 • COL1A1 • CTGF • CXCL10 • PACERR • PTGS2

Liraglutide improves senescence and ameliorating diabetic sarcopenia via the YAP-TAZ pathway. (PubMed, J Diabetes Complications) - "High glucose promotes muscle cell aging and sarcopenia, processes that liraglutide can attenuate by modulating the YAP/TAZ signaling pathway. This study underscores liraglutide's potential to alleviate muscle degeneration in diabetic sarcopenia through its regulatory impact on critical aging pathways."

Journal • Diabetes • Metabolic Disorders • Sarcopenia • Type 2 Diabetes Mellitus • CCND1 • CDKN1A • TP53

Prognostic Stratification of Epithelioid Pleural Mesothelioma Based on the Hippo-TEADs Network. (PubMed, Cancers (Basel)) - "Higher levels of downstream Hippo effectors are associated with poor response to platinum-pemetrexed doublet and worse OS. The stratification of ePM based on the activation of the YAP/TAZ-TEAD axis is an intriguing approach in the light of the inhibitors of this signaling that are currently under investigation."

Journal • Epithelioid Pleural Mesothelioma • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • VSIR • WWTR1 • YAP1

LATS1/2 inactivation in the mammary epithelium drives the evolution of a tumor-associated niche. (PubMed, EMBO Rep) - "We further show that inhibition of the YAP/TAZ-associated TEAD family of transcription factors blocks the development of the carcinomas and associated microenvironment. These observations demonstrate that carcinomas resulting from Hippo pathway dysregulation in the mammary epithelium are sufficient to drive cellular events that promote a basal-like tumor-associated niche and suggest that targeting dysregulated YAP/TAZ-TEAD activity may offer a therapeutic opportunity for basal-like mammary tumors."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • LATS1 • LATS2 • TGFB1

FAK mediates mechanical signaling to maintain epithelial homeostasis through YAP/TAZ-TEADs. (PubMed, Histochem Cell Biol) - "Finally, we used primary mouse epithelial cells to reconstruct the epithelium in vitro and found that FAK inhibition led to both a reduction in YAP/TAZ activity and an increase of differentiation in the basal layer cells. In conclusion, our findings reveal that FAK mediates mechanical signaling to maintain epithelial homeostasis via YAP/TAZ-TEADs."

Journal

The recent advances and implications in cancer therapy for the hippo pathway. (PubMed, Curr Opin Cell Biol) - "In this review, we discuss how the emerging role of biomolecular condensates regulates the activity of the pathway components, and how dysregulation of the pathway leads to cancer. Lastly, we highlight the therapeutic modalities which target YAP/TAZ-TEAD interaction for cancer therapy."

Journal • Review • Oncology

Distinct effects of Hippo-YAP/TAZ and YAP/TAZ-TEAD in epithelial maintenance and repair. (PubMed, Biochem Biophys Res Commun) - "These findings indicate that Hippo-mediated YAP/TAZ regulation may extend beyond TEAD-dependent transcription. Our work clarifies the distinct contributions of Hippo-YAP/TAZ signaling and YAP/TAZ-TEAD interaction to epithelial maintenance and provides a basis for the development of therapeutic strategies targeting YAP/TAZ in epithelial disorders."

Journal

Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis. (PubMed, Sci Adv) - "Thus, targeted therapies being developed against YAP/TAZ-TEAD are ineffective in macrophages. Together, our results introduce Golgi-associated TAZ as a potential molecular target for therapeutic intervention to treat tumor progression and chronic inflammatory diseases."

IO biomarker • Journal • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology

miR-424-5p Promotes Proliferation, Migration and Invasion of Colorectal Cancer Cells via the Targeting TXNIP/Hippo Axi. (PubMed, Int J Gen Med) - "And disordered Hippo pathway and YAP/TAZ-TEAD activity are related to tumor progression...The study clarify a novel miR-424-5p/TXNIP/Hippo signaling pathway that facilitated CRC cells proliferation, migration and invasion. The above findings suggested that miR-424-5p and TXNIP might serve as the potential therapeutic targets for CRC patients."

Journal • Acute Kidney Injury • Colorectal Cancer • Gastric Cancer • Genito-urinary Cancer • Hepatology • Kidney Cancer • Liver Cancer • Lung Cancer • Nephrology • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Renal Disease • Solid Tumor • MIR424 • TXNIP

Targeting YAP/TAZ-TEAD signaling as a therapeutic approach in head and neck squamous cell carcinoma. (PubMed, Cancer Lett) - "Here, we provide the pre-clinical evidence for the antitumor activity of novel smTEADi, SW-682 in HPV-negative HNSCC. A HNSCC-specific TEADi target gene set was defined from RNA-seq data, which is highly expressed in HNSCC tissues and predicts poor prognosis of HPV-negative HNSCC patients. Our results underscore that YAP/TAZ-TEAD-mediated growth-promoting programs represent a vulnerability in HPV-negative HNSCC, thus providing a pre-clinical rationale for the future evaluation of YAP/TAZ-TEAD targeting strategies as a therapeutic approach for HPV-negative HNSCC patients."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • FAT1 • WWTR1 • YAP1

Towards the design of ligands of the internal pocket TEADs C-terminal domain. (PubMed, Eur J Med Chem) - "Soaking with hTEAD2 gave seven new crystal structures where the ligands occupied palmitate pocket. 5-Benzyloxyindoles armed with vinylsulfamide moiety inhibit YAP/TAZ-TEAD target genes expression and breast cancer cell proliferation at micromolar concentration."

Journal • Breast Cancer • Oncology • Solid Tumor • TEAD2

YAP/TAZ Target Genes may Determine the Self-renewal and Survival of Glioblastoma Stem Cells (SNO 2024) - "Furthermore, our research has demonstrated that inhibiting YAP/TAZ activity with the drug Verteporfin induces apoptosis and promotes growth arrest in patient-derived EGFR-amplified/mutant glioblastoma models. Our findings highlight YAP/TAZ-TEAD as key mediators of glioblastoma stem cell (GSC) self-renewal and survival...Our research seeks to uncover the epigenetic basis of YAP/TAZ dependencies and to determine which genes and cellular processes are critical for tumor stem cell survival, tumor progression, and sensitivity to YAP/TAZ inhibition. These target genes could serve as biomarkers for predicting therapeutic response to YAP/TAZ inhibitors in glioblastoma."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • MYC • SOX2 • TAFAZZIN

Identification and Targeting of Tumor Driver Schwann(NF2loss) Cells in Sporadic and NF2-Related Vestibular Schwannomas (SNO 2024) - "We report that Schwann(NF2loss) cells are key tumor drivers in VS. These cells are highly proliferative (YAP/TAZ-TEAD axis), drive angiogenesis (VEGFA expression), and promote tumor mass accretion (macrophage influx via M-CSF/IL-34 pathway) that can all be targeted via TEAD inhibition."

Brain Cancer • Genetic Disorders • Neurofibromatosis • Oncology • Solid Tumor • CSF1 • EGFR • HIF1A • IL34 • NF2 • NRG1 • POSTN • TEAD1 • YAP1

Targeting of the YAP/TAZ-TEAD axis diminishes viability and differentiation potential in pediatric high-grade glioma (SNO 2024) - "Use of Verteporfin (VP), a FDA-approved YAP/TAZ small molecule inhibitor, mimicked the effects seen by YAP genetic depletion. Results from our work showing that YAP/TAZ-TEAD inhibition is a promising therapeutic avenue for management of pHGGs will be presented. Further pre-clinical work will follow to correlate observation and understand the therapeutic efficacy of YAP/TAZ-TEAD inhibition for pHGG treatment."

Clinical • Brain Cancer • CNS Tumor • Glioma • Malignant Glioma • Oncology • Pediatrics • Solid Tumor

Evaluating the Use of Merlin-YAP Dual-label Immunohistochemistry for Predicting Response to TEAD Inhibitor VT3989 (EORTC-NCI-AACR 2024) - P1/2 | "The Merlin/YAP duplex IHC assay is ready for clinical application in an ongoing VT3989 trial where clinical activity is being observed in mesothelioma and will provide novel insights on the YAP/TAZ-TEAD pathway."

Mesothelioma • Oncology • Solid Tumor • NF2

Advancements of anticancer agents by targeting the Hippo signalling pathway: biological activity, selectivity, docking analysis, and structure-activity relationship. (PubMed, Mol Divers) - "The YAP/TAZ-TEAD interaction leads to tumour development and the protein structure of YAP/TAZ-TEAD includes three interfaces and one hydrophobic pocket...We have also provided the various inhibitors under clinical and preclinical trials, and advancement of small molecules their detailed docking analysis, structure-activity relationship, and biological activity. We anticipate that the current study will be a helpful resource for researchers."

Journal • Review • Oncology

Targeting KRAS for pancreatic cancer treatment (AACRPanCa 2024) - "We have also identified YAP/TAZ-TEAD activation as a mechanism of acquired resistance and have characterized KEAP1 loss as a mechanism of primary resistance. Together, these studies have identified drug combination strategies that enhance KRAS inhibitor activity. Progress in these and other studies will be presented."

Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KEAP1 • KRAS

Activation of VGLL4 Suppresses Cardiomyocyte Maturational Hypertrophic Growth. (PubMed, Cells) - "To develop an in vitro model for studying CM maturational hypertrophy, we compared the biological effects of T3 (triiodothyronine), Dex (dexamethasone), and T3/Dex in cultured neonatal rat ventricular myocytes (NRVMs). On the molecular level, activation of VGLL4 inhibited the PI3K-AKT pathway, and disrupting VGLL4 and TEAD interaction abolished this inhibition. In conclusion, our data suggest that VGLL4 suppresses CM maturational hypertrophy by inhibiting the YAP/TAZ-TEAD complex and its downstream activation of the PI3K-AKT pathway."

Journal • VGLL4

High-dose methylprednisolone mediates YAP/TAZ-TEAD in vocal fold fibroblasts with macrophages. (PubMed, Res Sq) - "The pro-fibrotic effects of glucocorticoids may lead to a suboptimal therapeutic response for vocal fold (VF) pathology. Verteporfin attenuated upregulation of CCN2 , but not PTGS2 downregulation. High concentration methylprednisolone induced nuclear localization of S211-pGR and upregulated fibrotic genes mediated by YAP/TAZ activation."

Journal • Fibrosis • Immunology • Inflammation • Otorhinolaryngology • ACTA2 • COL1A1 • CTGF • CXCL10 • PACERR • PTGS2

Direct YAP/TAZ-TEAD inhibitor paves the way toward realizing cancer mechanomedicine. (PubMed, Pharmacol Res) - No abstract available

Journal • Oncology

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass. (PubMed, Nat Metab) - "Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription."

Journal • Lipodystrophy • Metabolic Disorders • LATS1 • LATS2 • LEP

Leveraging the Fragment Molecular Orbital and MM-GBSA Methods in Virtual Screening for the Discovery of Novel Non-Covalent Inhibitors Targeting the TEAD Lipid Binding Pocket. (PubMed, Int J Mol Sci) - "YAP/TAZ-TEAD facilitates the upregulation of multiple genes involved in evolutionary cell proliferation and survival...Subsequently, we optimized several analogs of BC-001 and found that the optimized compound BC-011 exhibited an IC50 of 72.43 nM. These findings can be used to design effective TEAD modulators with anticancer therapeutic implications."

Journal • Oncology • TEAD1