ArticleNature cancer2024
Direct and selective pharmacological disruption of the YAP-TEAD interface by IAG933 inhibits Hippo-dependent and RAS-MAPK-altered cancers.
Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 92 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
92 citing papers in PubMed, 114 citations in OpenAlex.
- Screening of peptide inhibitors targeting YAP-TEAD4 interaction: affinity evaluation and anti-AML cell activity.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- First-in-human phase Ia study of the covalent TEAD palmitoylation inhibitor BPI-460372 in patients with advanced solid tumors: pharmacokinetics, exposure-limited dosing, and early antitumor activity.Biomarker research · 2026Article
- YAP and WWTR1/TAZ Connect Mechanotransduction and Mitochondrial Metabolism in Cardiac Hypertrophy and Ventricular Remodeling.Journal of cardiovascular translational research · 2026Review
- Hippo Pathway-YAP/TAZ Signaling: Molecular Mechanisms, Biological Function, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Cell differentiation-related signaling pathways: biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Advancing clinical trials for rare renal cell carcinoma subtypes: Consensus statements from the International Kidney Cancer Symposium North America 2025 think tank.Urologic oncology · 2026Article
- Extracellular matrix reprogramming by the YAP/TAZ/TGF-β2 axis drives immune exclusion in cholangiocarcinoma models.The Journal of clinical investigation · 2026Article
- YAP-mediated mechanotransduction promotes hepatocellular carcinoma progression by targeting ATP1A1/CXCL1 axis.Acta pharmacologica Sinica · 2026Article
- The Crosstalk Between YAP/TAZ and Cancer Metabolism: From Mechanistic Insights to Drug Discovery.International journal of molecular sciences · 2026Review
- Targeting the lncRNA PVT-1-Hippo signaling axis in kidney diseases: an emerging therapeutic paradigm.Molecular biology reports · 2026Review
- Marine-Derived Fungal Metabolite MHO7 Promotes Breast Cancer Apoptosis as a Hippo Pathway Regulator by Modulating the YAP-TEAD Axis.Marine drugs · 2026Article
- Cancer stem cells are hyper-responsive sensors of the tumour microenvironment and regulate metastasis dynamics through YAP/TAZ.Nature cell biology · 2026Article
- Genetic Medicine Approaches for Tumor Suppressor Loss: Therapeutic Replacement with Self-Amplifying RNA.Pharmaceutical research · 2026Review
- The emerging role of the Hippo signaling pathway in interorgan crosstalk.The FEBS journal · 2026Review
- EDNRA Forms a Positive Feedback Loop with the Hippo/YAP Axis to Drive Triple-Negative Breast Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Transcription factor targeting strategies in cancer: mechanisms, challenges and cutting-edge progress.Acta pharmacologica Sinica · 2026Review
- Concurrent genetic and non-genetic resistance mechanisms to KRAS inhibition in colorectal cancer.Cancer cell · 2026Article
- Dissecting the oncogenic function of YAP1 and WWTR1 fusion proteins in mammary epithelial cells.Cancer letters · 2026Article
- TEAD inhibitor induced switch in energy metabolism drives human podocyte injury in vitro.Archives of toxicology · 2026Article
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
31 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The YAP-TEAD protein-protein interaction mediates YAP oncogenic functions downstream of the Hippo pathway. To date, available YAP-TEAD pharmacologic agents bind into the lipid pocket of TEAD, targeting the interaction indirectly via allosteric changes. However, the consequences of a direct pharmacological disruption of the interface between YAP and TEADs remain largely unexplored. Here, we present IAG933 and its analogs as potent first-in-class and selective disruptors of the YAP-TEAD protein-protein interaction with suitable properties to enter clinical trials. Pharmacologic abrogation of the interaction with all four TEAD paralogs resulted in YAP eviction from chromatin and reduced Hippo-mediated transcription and induction of cell death. In vivo, deep tumor regression was observed in Hippo-driven mesothelioma xenografts at tolerated doses in animal models as well as in Hippo-altered cancer models outside mesothelioma. Importantly this also extended to larger tumor indications, such as lung, pancreatic and colorectal cancer, in combination with RTK, KRAS-mutant selective and MAPK inhibitors, leading to more efficacious and durable responses. Clinical evaluation of IAG933 is underway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.