ArticleAmerican journal of cancer research2020
The novel potent TEAD inhibitor, K-975, inhibits YAP1/TAZ-TEAD protein-protein interactions and exerts an anti-tumor effect on malignant pleural mesothelioma.
Article in American journal of cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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Who cites it
110 citing papers in PubMed, 148 citations in OpenAlex.
- Hippo Pathway-YAP/TAZ Signaling: Molecular Mechanisms, Biological Function, Diseases, and Therapeutic Targets.MedComm · 2026Review
- The Crosstalk Between YAP/TAZ and Cancer Metabolism: From Mechanistic Insights to Drug Discovery.International journal of molecular sciences · 2026Review
- NUAK1 Inhibition Alleviates Ischemia-Reperfusion Injury via SYNE1-YAP1.Circulation research · 2026Article
- TEAD inhibitor induced switch in energy metabolism drives human podocyte injury in vitro.Archives of toxicology · 2026Article
- Covalent pan-TEAD inhibitors block YAP activity and demonstrate brain penetrance in a Hippo-dependent cancer model.Nature communications · 2026Article
- YAP/TAZ inhibition refines TGF-β signaling to prevent laryngeal fibrosis.bioRxiv : the preprint server for biology · 2026Article
- DPP-Mediated Interaction of TAZ/β-Catenin Promotes the Differentiation of DPSCs into Odontoblasts.International journal of molecular sciences · 2026Article
- Restoring the tumour mechanophenotype of vocal fold cancer reverts its malignant properties.Nature materials · 2026Article
- Two distinct modes of Vgll4-mediated Tead regulation control organ size in zebrafish.Communications biology · 2026Article
- Comprehensive analysis of TEAD inhibition in meningioma identifies MEK and mTOR inhibition as effective combination therapies against resistant lines.bioRxiv : the preprint server for biology · 2026Article
- Article
- Targeting cancer signaling pathways and their therapeutic strategies.Discover oncology · 2026Review
- Integrative Clinical and Molecular Evaluation of Renal Cell Carcinoma with Merlin Protein Deficiency and Biallelic Loss of NF2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Hippo-YAP/TAZ signaling in gastric cancer: molecular pathogenesis and emerging therapeutic horizons.Medical oncology (Northwood, London, England) · 2026Review
- YAP1::TFE3 mediates endothelial-to-mesenchymal plasticity in epithelioid hemangioendothelioma.Molecular oncology · 2026Article
- CRISPR screens reveal YAP/TEAD axis as a mediator of drug-tolerant cells in EGFR-mutant NSCLC.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- YAP1 Is a Crucial Nexus in the Tumor Microenvironment.Current medical science · 2026Review
- Fungal commensal promotes intestinal repair via its secreted peptide in mice.Nature microbiology · 2026Article
- Degradation of the TEAD•YAP/TAZ Transcription Factor Complex by Heterobifunctional Small Molecules that Bind to the TEAD Allosteric Lipid Pocket.bioRxiv : the preprint server for biology · 2026Article
- Targeting YAP-TEAD Interaction with Honokiol to Inhibit Melanoma Progression and Metastasis.Biomolecules & therapeutics · 2026Article
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hippo signaling pathway regulates cell fate and organ development. In the Hippo pathway, transcriptional enhanced associate domain (TEAD) which is a transcription factor is activated by forming a complex with yes-associated protein 1 (YAP1) or transcriptional coactivator with PDZ-binding motif (TAZ, also called WWTR1). Hyper-activation of YAP1/TAZ, leading to the activation of TEAD, has been reported in many cancers, including malignant pleural mesothelioma (MPM). Therefore, the YAP1/TAZ-TEAD complex is considered a novel therapeutic target for cancer treatment. However, few reports have described YAP1/TAZ-TEAD inhibitors, and their efficacy and selectivity are poor. In this study, we performed a high-throughput screening of a neurofibromin 2 (NF2)-deficient MPM cell line and a large tumor suppressor kinase 1/2 (LATS1/2)-deficient non-small-cell lung cancer cell line using a transcriptional reporter assay. After screening and optimization, K-975 was successfully identified as a potent inhibitor of YAP1/TAZ-TEAD signaling. X-ray crystallography revealed that K-975 was covalently bound to an internal cysteine residue located in the palmitate-binding pocket of TEAD. K-975 had a strong inhibitory effect against protein-protein interactions between YAP1/TAZ and TEAD in cell-free and cell-based assays. Furthermore, K-975 potently inhibited the proliferation of NF2-non-expressing MPM cell lines compared with NF2-expressing MPM cell lines. K-975 also suppressed tumor growth and provided significant survival benefit in MPM xenograft models. These findings indicate that K-975 is a strong and selective TEAD inhibitor with the potential to become an effective drug candidate for MPM therapy.
Indexed as
Identifiers
33415007PMC7783735W3119859826What OpenQuestion holds
Registered trials
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.