CINXE.COM
Development of a pipeline to evaluate YAP-TEAD inhibitor potential - direct TEAD inhibition represses cancerous growth in a NF2-mutant model of mesothelioma | bioRxiv
<!DOCTYPE html> <html lang="en" dir="ltr" xmlns="http://www.w3.org/1999/xhtml" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#" > <!--[if IE]><![endif]--> <link rel="dns-prefetch" href="//d33xdlntwy0kbs.cloudfront.net" /> <link rel="dns-prefetch" href="//www.google.com" /> <link rel="dns-prefetch" href="//scholar.google.com" /> <link rel="dns-prefetch" href="//www.googletagmanager.com" /> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <link rel="shortcut icon" href="https://www.biorxiv.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="/content/10.1101/2024.11.12.622964v1.full.pdf" /> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/10.1101/2024.11.12.622964v1.full.txt" /> <meta name="article_thumbnail" content="https://www.biorxiv.org/content/biorxiv/early/2024/11/12/2024.11.12.622964/embed/graphic-5.gif" /> <meta name="type" content="article" /> <meta name="category" content="article" /> <meta name="HW.identifier" content="/biorxiv/early/2024/11/12/2024.11.12.622964.atom" /> <meta name="HW.pisa" content="biorxiv;2024.11.12.622964v1" /> <meta name="DC.Format" content="text/html" /> <meta name="DC.Language" content="en" /> <meta name="DC.Title" content="Development of a pipeline to evaluate YAP-TEAD inhibitor potential - direct TEAD inhibition represses cancerous growth in a NF2-mutant model of mesothelioma" /> <meta name="DC.Identifier" content="10.1101/2024.11.12.622964" /> <meta name="DC.Date" content="2024-11-12" /> <meta name="DC.Publisher" content="Cold Spring Harbor Laboratory" /> <meta name="DC.Rights" content="© 2024, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution 4.0 International), CC BY 4.0, as described at http://creativecommons.org/licenses/by/4.0/" /> <meta name="DC.AccessRights" content="restricted" /> <meta name="DC.Description" content="As the core, tumorigenic downstream effectors of the Hippo signalling pathway, YAP/TAZ and the TEAD family of transcription factors represent attractive targets for drug discovery efforts within cancer research. This is particularly true within the context of pleural mesothelioma, in which there are many recent preclinical developments and clinical trials evaluating the efficacy of TEAD inhibitors. The range of inhibitors have shown great promise, but comparisons of their performances are so far limited. Here we develop a high content pipeline that enables a comparative analysis of currently developed YAP/TAZ-TEAD inhibitors. We take advantage of isogenic cellular models that enable us to examine inhibitor specificity. We identify genetic compensation of the Hippo pathway transcriptional module, with implications for therapeutic targeting, and implement Cell Painting to develop a detailed morphological profiling pipeline that enables further characterisation, quantification, and analysis of off-target effects. Our pipeline is scalable and allows us to establish specificity and comparative potency within cancer relevant assays in a clinically relevant cellular model. ### Competing Interest Statement The authors have declared no competing interest." /> <meta name="DC.Contributor" content="Richard Cunningham" /> <meta name="DC.Contributor" content="Siyang Jia" /> <meta name="DC.Contributor" content="Krishna Purohit" /> <meta name="DC.Contributor" content="Michaela Noskova Fairley" /> <meta name="DC.Contributor" content="Yue Lin" /> <meta name="DC.Contributor" content="Ning Sze Hui" /> <meta name="DC.Contributor" content="Rebecca E. Graham" /> <meta name="DC.Contributor" content="Adriano G. Rossi" /> <meta name="DC.Contributor" content="Justyna Cholewa-Waclaw" /> <meta name="DC.Contributor" content="Neil O. Carragher" /> <meta name="DC.Contributor" content="Carsten Gram Hansen" /> <meta name="article:published_time" content="2024-11-12" /> <meta name="article:section" content="New Results" /> <meta name="citation_title" content="Development of a pipeline to evaluate YAP-TEAD inhibitor potential - direct TEAD inhibition represses cancerous growth in a NF2-mutant model of mesothelioma" /> <meta name="citation_abstract" lang="en" content="<p>As the core, tumorigenic downstream effectors of the Hippo signalling pathway, YAP/TAZ and the TEAD family of transcription factors represent attractive targets for drug discovery efforts within cancer research. This is particularly true within the context of pleural mesothelioma, in which there are many recent preclinical developments and clinical trials evaluating the efficacy of TEAD inhibitors. The range of inhibitors have shown great promise, but comparisons of their performances are so far limited. Here we develop a high content pipeline that enables a comparative analysis of currently developed YAP/TAZ-TEAD inhibitors. We take advantage of isogenic cellular models that enable us to examine inhibitor specificity. We identify genetic compensation of the Hippo pathway transcriptional module, with implications for therapeutic targeting, and implement Cell Painting to develop a detailed morphological profiling pipeline that enables further characterisation, quantification, and analysis of off-target effects. Our pipeline is scalable and allows us to establish specificity and comparative potency within cancer relevant assays in a clinically relevant cellular model.</p>" /> <meta name="citation_journal_title" content="bioRxiv" /> <meta name="citation_publisher" content="Cold Spring Harbor Laboratory" /> <meta name="citation_publication_date" content="2024/01/01" /> <meta name="citation_mjid" content="biorxiv;2024.11.12.622964v1" /> <meta name="citation_id" content="2024.11.12.622964v1" /> <meta name="citation_public_url" content="https://www.biorxiv.org/content/10.1101/2024.11.12.622964v1" /> <meta name="citation_abstract_html_url" content="https://www.biorxiv.org/content/10.1101/2024.11.12.622964v1.abstract" /> <meta name="citation_full_html_url" content="https://www.biorxiv.org/content/10.1101/2024.11.12.622964v1.full" /> <meta name="citation_pdf_url" content="https://www.biorxiv.org/content/biorxiv/early/2024/11/12/2024.11.12.622964.full.pdf" /> <meta name="citation_doi" content="10.1101/2024.11.12.622964" /> <meta name="citation_num_pages" content="33" /> <meta name="citation_article_type" content="Article" /> <meta name="citation_section" content="New Results" /> <meta name="citation_firstpage" content="2024.11.12.622964" /> <meta name="citation_author" content="Richard Cunningham" /> <meta name="citation_author_institution" content="University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair" /> <meta name="citation_author_orcid" content="http://orcid.org/0000-0003-4127-8917" /> <meta name="citation_author" content="Siyang Jia" /> <meta name="citation_author_institution" content="University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair" /> <meta name="citation_author" content="Krishna Purohit" /> <meta name="citation_author_institution" content="University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair" /> <meta name="citation_author" content="Michaela Noskova Fairley" /> <meta name="citation_author_institution" content="University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair" /> <meta name="citation_author_orcid" content="http://orcid.org/0000-0003-2055-0221" /> <meta name="citation_author" content="Yue Lin" /> <meta name="citation_author_institution" content="University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair" /> <meta name="citation_author" content="Ning Sze Hui" /> <meta name="citation_author_institution" content="University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair" /> <meta name="citation_author_orcid" content="http://orcid.org/0000-0002-5447-9569" /> <meta name="citation_author" content="Rebecca E. Graham" /> <meta name="citation_author_institution" content="Centre for Clinical Brain Sciences, Anne Rowling Regenerative Neurology Clinic, University of Edinburgh" /> <meta name="citation_author_orcid" content="http://orcid.org/0000-0002-0590-4135" /> <meta name="citation_author" content="Adriano G. Rossi" /> <meta name="citation_author_institution" content="University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair" /> <meta name="citation_author_orcid" content="http://orcid.org/0000-0003-3173-9521" /> <meta name="citation_author" content="Justyna Cholewa-Waclaw" /> <meta name="citation_author_institution" content="High Content Screening Facility, Institute for Regeneration and Repair, The University of Edinburgh" /> <meta name="citation_author" content="Neil O. Carragher" /> <meta name="citation_author_institution" content="Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh" /> <meta name="citation_author_orcid" content="http://orcid.org/0000-0001-5541-9747" /> <meta name="citation_author" content="Carsten Gram Hansen" /> <meta name="citation_author_institution" content="University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair" /> <meta name="citation_author_email" content="carsten.g.hansen@ed.ac.uk" /> <meta name="citation_author_orcid" content="http://orcid.org/0000-0003-0746-7482" /> <meta name="citation_reference" content="Wagner, J. C., Sleggs, C. A. & Marchand, P. Diffuse Pleural Mesothelioma and Asbestos Exposure in the North Western Cape Province. Occup. Environ. Med. 17, 260–271 (1960)." /> <meta name="citation_reference" content="Mirra, L. et al. Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma. Curr. Med. Chem. (2024) doi:10.2174/0109298673268206240405084558." /> <meta name="citation_reference" content="Nowak, A. K., Jackson, A. & Sidhu, C. Management of Advanced Pleural Mesothelioma—At the Crossroads. JCO Oncol. Pract. 18, 116–124 (2022)." /> <meta name="citation_reference" content="Tsao, A. S., Pass, H. I., Rimner, A. & Mansfield, A. S. New Era for Malignant Pleural Mesothelioma: Updates on Therapeutic Options. J. Clin. Oncol. 40, 681–692 (2022)." /> <meta name="citation_reference" content="Jin, H., Wang, L. & Bernards, R. Rational combinations of targeted cancer therapies: background, advances and challenges. Nat. Rev. Drug Discov. 22, 213–234 (2023)." /> <meta name="citation_reference" content="Cunningham, R. et al. YAP/TAZ activation predicts clinical outcomes in mesothelioma and is conserved in in vitro model of driver mutations. Clin. Transl. Med. 13, e1190 (2023)." /> <meta name="citation_reference" content="Bueno, R. et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat. Genet. 48, 407–416 (2016)." /> <meta name="citation_reference" content="Hmeljak, J. et al. Integrative Molecular Characterization of Malignant Pleural Mesothelioma. Cancer Discov. 8, 1548–1565 (2018)." /> <meta name="citation_reference" content="Mangiante, L. et al. Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity. Nat. Genet. 55, 607–618 (2023)." /> <meta name="citation_reference" content="Febres-Aldana, C. A. et al. Diffuse Pleural Mesothelioma: Advances in Molecular Pathogenesis, Diagnosis, and Treatment. Annu. Rev. Pathol. Mech. Dis. 19, 11–42 (2024)." /> <meta name="citation_reference" content="Rausch, V. & Hansen, C. G. The Hippo Pathway, YAP/TAZ, and the Plasma Membrane. Trends Cell Biol. 30, 32–48 (2020)." /> <meta name="citation_reference" content="Hansen, C. G., Moroishi, T. & Guan, K.-L. YAP and TAZ: a nexus for Hippo signaling and beyond. Trends Cell Biol. 25, 499–513 (2015)." /> <meta name="citation_reference" content="Currey, L., Thor, S. & Piper, M. TEAD family transcription factors in development and disease. Development 148, (2021)." /> <meta name="citation_reference" content="Lin, K. C. et al. Regulation of Hippo pathway transcription factor TEAD by p38 MAPK-induced cytoplasmic translocation. Nat. Cell Biol. 19, 996–1002 (2017)." /> <meta name="citation_reference" content="Davis, J. R. & Tapon, N. Hippo signalling during development. Development 146, (2019)." /> <meta name="citation_reference" content="Zhong, Z., Jiao, Z. & Yu, F.-X. The Hippo signaling pathway in development and regeneration. Cell Rep. 43, 113926 (2024)." /> <meta name="citation_reference" content="Lamar, J. M. et al. The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain. Proc. Natl. Acad. Sci. 109, E2441–E2450 (2012)." /> <meta name="citation_reference" content="Feng, X. et al. Hippo-Independent Activation of YAP by the GNAQ Uveal Melanoma Oncogene through a Trio-Regulated Rho GTPase Signaling Circuitry. Cancer Cell 25, 831–845 (2014)." /> <meta name="citation_reference" content="Sorrentino, G. et al. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat. Cell Biol. 16, 357–366 (2014)." /> <meta name="citation_reference" content="Calvo, F. et al. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat. Cell Biol. 15, 637–46 (2013)." /> <meta name="citation_reference" content="Shao, D. D. et al. KRAS and YAP1 Converge to Regulate EMT and Tumor Survival. Cell 158, 171–184 (2014)." /> <meta name="citation_reference" content="Lau, A. N. et al. Tumor-propagating cells and Yap/Taz activity contribute to lung tumor progression and metastasis. EMBO J. 33, 468–81 (2014)." /> <meta name="citation_reference" content="Seavey, C. N. et al. WWTR1 (TAZ)-CAMTA1 gene fusion is sufficient to dysregulate YAP/TAZ signaling and drive epithelioid hemangioendothelioma tumorigenesis. Genes Dev. 35, 512–527 (2021)." /> <meta name="citation_reference" content="Driskill, J. H. et al. WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma. Genes Dev. 35, 495–511 (2021)." /> <meta name="citation_reference" content="Moroishi, T., Hansen, C. G. & Guan, K.-L. The emerging roles of YAP and TAZ in cancer. Nat. Rev. Cancer 15, 73–79 (2015)." /> <meta name="citation_reference" content="Noland, C. L. et al. Palmitoylation of TEAD Transcription Factors Is Required for Their Stability and Function in Hippo Pathway Signaling. Structure 24, 179–186 (2016)." /> <meta name="citation_reference" content="Chan, P. et al. Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway. Nat. Chem. Biol. 12, 282–289 (2016)." /> <meta name="citation_reference" content="Lim, E. et al. Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial. Lancet. Respir. Med. 12, 457–466 (2024)." /> <meta name="citation_reference" content="Cunningham, R. & Hansen, C. G. The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer. Clin. Sci. 136, 197–222 (2022)." /> <meta name="citation_reference" content="Pichot, C. S. et al. Dasatinib synergizes with doxorubicin to block growth, migration, and invasion of breast cancer cells. Br. J. Cancer 101, 38–47 (2009)." /> <meta name="citation_reference" content="Nam, S. et al. Action of the Src Family Kinase Inhibitor, Dasatinib (BMS-354825), on Human Prostate Cancer Cells. Cancer Res. 65, 9185–9189 (2005)." /> <meta name="citation_reference" content="Liu-Chittenden, Y. et al. Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. Genes Dev. 26, 1300–5 (2012)." /> <meta name="citation_reference" content="Dasari, V. R. et al. Verteporfin exhibits YAP-independent anti-proliferative and cytotoxic effects in endometrial cancer cells. Oncotarget 8, 28628–28640 (2017)." /> <meta name="citation_reference" content="Xia, Y., Sun, M., Huang, H. & Jin, W.-L. Drug repurposing for cancer therapy. Signal Transduct. Target. Ther. 9, 92 (2024)." /> <meta name="citation_reference" content="Franklin, J. M., Wu, Z. & Guan, K.-L. Insights into recent findings and clinical application of YAP and TAZ in cancer. Nat. Rev. Cancer 23, 512–525 (2023)." /> <meta name="citation_reference" content="Tang, T. T. et al. Small Molecule Inhibitors of TEAD Auto-palmitoylation Selectively Inhibit Proliferation and Tumor Growth of NF2-deficient Mesothelioma. Mol. Cancer Ther. 20, 986–998 (2021)." /> <meta name="citation_reference" content="Kaneda, A. et al. The novel potent TEAD inhibitor, K-975, inhibits YAP1/TAZ-TEAD protein-protein interactions and exerts an anti-tumor effect on malignant pleural mesothelioma. Am. J. Cancer Res. 10, 4399–4415 (2020)." /> <meta name="citation_reference" content="Kaneda, A. et al. Abstract 3086: Discovery of a first-in-class TEAD inhibitor which directly inhibits YAP/TAZ-TEAD protein-protein interaction and shows a potent anti-tumor effect in malignant pleural mesothelioma. Cancer Res. 79, 3086–3086 (2019)." /> <meta name="citation_reference" content="Amidon, B. S. et al. Abstract 2156: IK-930 is a novel TEAD inhibitor for the treatment of cancers harboring mutations in the Hippo signal transduction pathway. Cancer Res. 82, 2156–2156 (2022)." /> <meta name="citation_reference" content="Tolcher, A. W. et al. A phase 1, first-in-human study of IK-930, an oral TEAD inhibitor targeting the Hippo pathway in subjects with advanced solid tumors. J. Clin. Oncol. 40, TPS3168–TPS3168 (2022)." /> <meta name="citation_reference" content="Pobbati, A. V & Hong, W. A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy. Theranostics 10, 3622–3635 (2020)." /> <meta name="citation_reference" content="Wang, C. et al. Verteporfin inhibits YAP function through up-regulating 14-3-3σ sequestering YAP in the cytoplasm. Am. J. Cancer Res. 6, 27–37 (2016)." /> <meta name="citation_reference" content="Sun, J. et al. A tightly controlled Src-YAP signaling axis determines therapeutic response to dasatinib in renal cell carcinoma. Theranostics 8, 3256–3267 (2018)." /> <meta name="citation_reference" content="Hsu, P.-C., Yang, C.-T., Jablons, D. M. & You, L. The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC). Cancers (Basel). 12, 1361 (2020)." /> <meta name="citation_reference" content="Wang, Z. et al. Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility. Proc. Natl. Acad. Sci. U. S. A. 111, E89–98 (2014)." /> <meta name="citation_reference" content="Wang, Y. et al. Comprehensive Molecular Characterization of the Hippo Signaling Pathway in Cancer. Cell Rep. 25, 1304–1317.e5 (2018)." /> <meta name="citation_reference" content="Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protoc. 8, 2281–2308 (2013)." /> <meta name="citation_reference" content="Hao, Y., Chun, A., Cheung, K., Rashidi, B. & Yang, X. Tumor Suppressor LATS1 Is a Negative Regulator of Oncogene YAP. J. Biol. Chem. 283, 5496–5509 (2008)." /> <meta name="citation_reference" content="Zhao, B., Li, L., Tumaneng, K., Wang, C.-Y. & Guan, K.-L. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). Genes Dev. 24, 72–85 (2010)." /> <meta name="citation_reference" content="Kim, N.-G., Koh, E., Chen, X. & Gumbiner, B. M. E-cadherin mediates contact inhibition of proliferation through Hippo signaling-pathway components. Proc. Natl. Acad. Sci. 108, 11930–11935 (2011)." /> <meta name="citation_reference" content="Zhao, B. et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 21, 2747–61 (2007)." /> <meta name="citation_reference" content="Hao, S. et al. YAP condensates are highly organized hubs. iScience 27, 109927 (2024)." /> <meta name="citation_reference" content="Yu, F.-X. et al. Regulation of the Hippo-YAP Pathway by G-Protein-Coupled Receptor Signaling. Cell 150, 780–791 (2012)." /> <meta name="citation_reference" content="Meng, Z. et al. MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway. Nat. Commun. 6, 8357 (2015)." /> <meta name="citation_reference" content="Park, H. W. et al. Alternative Wnt Signaling Activates YAP/TAZ. Cell 162, 780–94 (2015)." /> <meta name="citation_reference" content="Moroishi, T. et al. A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis. Genes Dev. 29, 1271–84 (2015)." /> <meta name="citation_reference" content="Evsen, L., Morris, P. J., Thomas, C. J. & Ceribelli, M. Comparative Assessment and High-Throughput Drug-Combination Profiling of TEAD-Palmitoylation Inhibitors in Hippo Pathway Deficient Mesothelioma. Pharmaceuticals (Basel). 16, (2023)." /> <meta name="citation_reference" content="Ishiguro, T. et al. Tumor-derived spheroids: Relevance to cancer stem cells and clinical applications. Cancer Sci. 108, 283–289 (2017)." /> <meta name="citation_reference" content="Zhao, B. et al. Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev. 26, 54–68 (2012)." /> <meta name="citation_reference" content="Muller, F. et al. Abstract 445: A next generation TEAD inhibitor with refined isoform specificity for superior safety &amp; efficacy. Cancer Res. 83, 445–445 (2023)." /> <meta name="citation_reference" content="Muller, F., Kunnimalaiyaan, S., Mangrolia, P. & Olson, J. Abstract 5913: TEAD1/4 inhibitors exhibit deeper biological impact and broader activity compared to TEAD1-only inhibitors in both monotherapy and combination without additional kidney toxicity. Cancer Res. 84, 5913–5913 (2024)." /> <meta name="citation_reference" content="Knight, J. F. et al. TEAD1 and c-Cbl are novel prostate basal cell markers that correlate with poor clinical outcome in prostate cancer. Br. J. Cancer 99, 1849–1858 (2008)." /> <meta name="citation_reference" content="Lu, T. et al. Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3. Acta Pharm. Sin. B 11, 3206–3219 (2021)." /> <meta name="citation_reference" content="Zhang, W. et al. TEAD4 overexpression promotes epithelial-mesenchymal transition and associates with aggressiveness and adverse prognosis in head neck squamous cell carcinoma. Cancer Cell Int. 18, 178 (2018)." /> <meta name="citation_reference" content="Sun, D., Gao, W., Hu, H. & Zhou, S. Why 90% of clinical drug development fails and how to improve it? Acta Pharm. Sin. B 12, 3049–3062 (2022)." /> <meta name="citation_reference" content="Seyhan, A. A. Lost in translation: the valley of death across preclinical and clinical divide – identification of problems and overcoming obstacles. Transl. Med. Commun. 4, 18 (2019)." /> <meta name="citation_reference" content="Lin, A. et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci. Transl. Med. 11, (2019)." /> <meta name="citation_reference" content="Lechner, S. et al. Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target. Nat. Chem. Biol. 18, 812–820 (2022)." /> <meta name="citation_reference" content="Calizo, R. C. et al. Disruption of podocyte cytoskeletal biomechanics by dasatinib leads to nephrotoxicity. Nat. Commun. 10, 2061 (2019)." /> <meta name="citation_reference" content="Perlman, Z. E. et al. Multidimensional drug profiling by automated microscopy. Science 306, 1194–8 (2004)." /> <meta name="citation_reference" content="Chandrasekaran, S. N. et al. JUMP Cell Painting dataset: morphological impact of 136,000 chemical and genetic perturbations. bioRxiv 2023.03.23.534023 (2023) doi:10.1101/2023.03.23.534023." /> <meta name="citation_reference" content="Tian, G., Harrison, P. J., Sreenivasan, A. P., Carreras-Puigvert, J. & Spjuth, O. Combining molecular and cell painting image data for mechanism of action prediction. Artif. Intell. Life Sci. 3, 100060 (2023)." /> <meta name="citation_reference" content="Fredin Haslum, J., et al. Cell Painting-based bioactivity prediction boosts high-throughput screening hit-rates and compound diversity. Nat. Commun. 15, 3470 (2024)." /> <meta name="citation_reference" content="Stossi, F. et al. High throughput microscopy and single cell phenotypic image-based analysis in toxicology and drug discovery. Biochem. Pharmacol. 216, 115770 (2023)." /> <meta name="citation_reference" content="Garcia de Lomana, M., Marin Zapata, P. A. & Montanari, F. Predicting the Mitochondrial Toxicity of Small Molecules: Insights from Mechanistic Assays and Cell Painting Data. Chem. Res. Toxicol. 36, 1107–1120 (2023)." /> <meta name="citation_reference" content="Cimini, B. A. et al. Optimizing the Cell Painting assay for image-based profiling. Nat. Protoc. 18, 1981–2013 (2023)." /> <meta name="citation_reference" content="Giotti, B. et al. Single cell view of tumor microenvironment gradients in pleural mesothelioma. Cancer Discov. (2024) doi:10.1158/2159-8290.CD-23-0017." /> <meta name="citation_reference" content="Ma, X. et al. Spatial Landscape of Malignant Pleural and Peritoneal Mesothelioma Tumor Immune Microenvironments. Cancer Res. Commun. 4, 2133–2146 (2024)." /> <meta name="citation_reference" content="Dudek, A. Z. et al. Phase II Study of Dasatinib in Patients with Previously Treated Malignant Mesothelioma (Cancer and Leukemia Group B 30601): A Brief Report. J. Thorac. Oncol. 7, 755–759 (2012)." /> <meta name="citation_reference" content="Pobbati, A. V, Kumar, R., Rubin, B. P. & Hong, W. Therapeutic targeting of TEAD transcription factors in cancer. Trends Biochem. Sci. 48, 450–462 (2023)." /> <meta name="citation_reference" content="Mazzocchi, A. R., Rajan, S. A. P., Votanopoulos, K. I., Hall, A. R. & Skardal, A. In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening. Sci. Rep. 8, 2886 (2018)." /> <meta name="citation_reference" content="Hocking, A. J., Mortimer, L. A., Farrall, A. L., Russell, P. A. & Klebe, S. Establishing mesothelioma patient-derived organoid models from malignant pleural effusions. Lung Cancer 191, 107542 (2024)." /> <meta name="citation_reference" content="Young, N. et al. Abstract 1646: IK-930, a paralog-selective TEAD inhibitor for treating YAP/TAZ-TEAD dependent cancers. Cancer Res. 83, 1646–1646 (2023)." /> <meta name="citation_reference" content="Ikena Oncology Announces Strategic Update. (2024)." /> <meta name="citation_reference" content="Chapeau, E. A. et al. Direct and selective pharmacological disruption of the YAP–TEAD interface by IAG933 inhibits Hippo-dependent and RAS–MAPK-altered cancers. Nat. Cancer 5, 1102–1120 (2024)." /> <meta name="citation_reference" content="Moffat, J. G., Rudolph, J. & Bailey, D. Phenotypic screening in cancer drug discovery — past, present and future. Nat. Rev. Drug Discov. 13, 588–602 (2014)." /> <meta name="citation_reference" content="Hansen, C. G., Ng, Y. L. D., Lam, W.-L. M., Plouffe, S. W. & Guan, K.-L. The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC1. Cell Res. 25, 1299–1313 (2015)." /> <meta name="citation_reference" content="Rausch, V. et al. The Hippo Pathway Regulates Caveolae Expression and Mediates Flow Response via Caveolae. Curr. Biol. 29, 242–255.e6 (2019)." /> <meta name="citation_reference" content="Spandidos, A., Wang, X., Wang, H. & Seed, B. PrimerBank: a resource of human and mouse PCR primer pairs for gene expression detection and quantification. Nucleic Acids Res. 38, D792–9 (2010)." /> <meta name="citation_reference" content="Stirling, D. R. et al. CellProfiler 4: improvements in speed, utility and usability. BMC Bioinformatics 22, 433 (2021)." /> <meta name="citation_reference" content="Stringer, C., Wang, T., Michaelos, M. & Pachitariu, M. Cellpose: a generalist algorithm for cellular segmentation. Nat. Methods 18, 100–106 (2021)." /> <meta name="citation_reference" content="Chandrasekaran, S. N. et al. Three million images and morphological profiles of cells treated with matched chemical and genetic perturbations. Nat. Methods 21, 1114–1121 (2024)." /> <meta name="citation_reference" content="Singh, S., et al. Cytominer: Methods for Image-Based Cell Profiling. at https://cran.r-project.org/package=cytominer (2020)." /> <meta name="citation_reference" content="Gu, Z., Gu, L., Eils, R., Schlesner, M. & Brors, B. circlize Implements and enhances circular visualization in R. Bioinformatics 30, 2811–2 (2014)." /> <meta name="twitter:title" content="Development of a pipeline to evaluate YAP-TEAD inhibitor potential - direct TEAD inhibition represses cancerous growth in a NF2-mutant model of mesothelioma" /> <meta name="twitter:site" content="@biorxivpreprint" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:image" content="https://www.biorxiv.org/sites/default/files/images/biorxiv_logo_homepage7-5-small.png" /> <meta name="twitter:description" content="As the core, tumorigenic downstream effectors of the Hippo signalling pathway, YAP/TAZ and the TEAD family of transcription factors represent attractive targets for drug discovery efforts within cancer research. This is particularly true within the context of pleural mesothelioma, in which there are many recent preclinical developments and clinical trials evaluating the efficacy of TEAD inhibitors. The range of inhibitors have shown great promise, but comparisons of their performances are so far limited. Here we develop a high content pipeline that enables a comparative analysis of currently developed YAP/TAZ-TEAD inhibitors. We take advantage of isogenic cellular models that enable us to examine inhibitor specificity. We identify genetic compensation of the Hippo pathway transcriptional module, with implications for therapeutic targeting, and implement Cell Painting to develop a detailed morphological profiling pipeline that enables further characterisation, quantification, and analysis of off-target effects. Our pipeline is scalable and allows us to establish specificity and comparative potency within cancer relevant assays in a clinically relevant cellular model. ### Competing Interest Statement The authors have declared no competing interest." /> <meta name="og-title" property="og:title" content="Development of a pipeline to evaluate YAP-TEAD inhibitor potential - direct TEAD inhibition represses cancerous growth in a NF2-mutant model of mesothelioma" /> <meta name="og-url" property="og:url" content="https://www.biorxiv.org/content/10.1101/2024.11.12.622964v1" /> <meta name="og-site-name" property="og:site_name" content="bioRxiv" /> <meta name="og-description" property="og:description" content="As the core, tumorigenic downstream effectors of the Hippo signalling pathway, YAP/TAZ and the TEAD family of transcription factors represent attractive targets for drug discovery efforts within cancer research. This is particularly true within the context of pleural mesothelioma, in which there are many recent preclinical developments and clinical trials evaluating the efficacy of TEAD inhibitors. The range of inhibitors have shown great promise, but comparisons of their performances are so far limited. Here we develop a high content pipeline that enables a comparative analysis of currently developed YAP/TAZ-TEAD inhibitors. We take advantage of isogenic cellular models that enable us to examine inhibitor specificity. We identify genetic compensation of the Hippo pathway transcriptional module, with implications for therapeutic targeting, and implement Cell Painting to develop a detailed morphological profiling pipeline that enables further characterisation, quantification, and analysis of off-target effects. Our pipeline is scalable and allows us to establish specificity and comparative potency within cancer relevant assays in a clinically relevant cellular model. ### Competing Interest Statement The authors have declared no competing interest." /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="https://www.biorxiv.org/sites/default/files/images/biorxiv_logo_homepage7-5-small.png" /> <meta name="citation_date" content="2024-11-12" /> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/10.1101/2024.11.12.622964v1.ppt" /> <meta name="description" content="bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution" /> <meta name="generator" content="Drupal 7 (http://drupal.org)" /> <link rel="canonical" href="https://www.biorxiv.org/content/10.1101/2024.11.12.622964v1" /> <link rel="shortlink" href="https://www.biorxiv.org/node/4217464" /> <title>Development of a pipeline to evaluate YAP-TEAD inhibitor potential - direct TEAD inhibition represses cancerous growth in a NF2-mutant model of mesothelioma | bioRxiv</title> <link type="text/css" rel="stylesheet" href="https://www.biorxiv.org/sites/default/files/advagg_css/css__7SC0i-kTgUlQGKuqbmyS18Sez8FDO-aG9FSHkGrLGl8__EBUojqg5W_1M2-aUl2Y1w9JxEEauoJ0pj29wOb-7Vz4__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.css" media="all" /> <link type="text/css" rel="stylesheet" href="//cdn.jsdelivr.net/qtip2/2.2.1/jquery.qtip.min.css" media="all" /> <link type="text/css" rel="stylesheet" href="https://www.biorxiv.org/sites/default/files/advagg_css/css__UufzdoKtMhzTNiAJfsa_0bYn78zz-bBHwNEqMQ0UIXk__1-Opexvnkee5dlO1d6qLW5_7DT6gOdNGKRcC-FxT6QU__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.css" media="all" /> <style type="text/css" media="all"> /* <![CDATA[ */ .panels-flexible-new .panels-flexible-region{padding:0}.panels-flexible-new .panels-flexible-region-inside{padding-right:.5em;padding-left:.5em}.panels-flexible-new .panels-flexible-region-inside-first{padding-left:0}.panels-flexible-new .panels-flexible-region-inside-last{padding-right:0}.panels-flexible-new .panels-flexible-column{padding:0}.panels-flexible-new .panels-flexible-column-inside{padding-right:.5em;padding-left:.5em}.panels-flexible-new .panels-flexible-column-inside-first{padding-left:0}.panels-flexible-new .panels-flexible-column-inside-last{padding-right:0}.panels-flexible-new .panels-flexible-row{padding:0 0 .5em;margin:0}.panels-flexible-new .panels-flexible-row-last{padding-bottom:0}.panels-flexible-column-new-main{float:left;width:99.0000%}.panels-flexible-new-inside{padding-right:0}.panels-flexible-new{width:auto}.panels-flexible-region-new-center{float:left;width:99.0000%}.panels-flexible-row-new-main-row-inside{padding-right:0} /* ]]> */ </style> <link type="text/css" rel="stylesheet" href="https://www.biorxiv.org/sites/default/files/advagg_css/css__PWuQ_RYRTJ4BLEKsbWQeHysPg0gOQ3571ruQa_rXvAo__pWyBeQHtoijrNnOoDz9ZPdiNPirDrSCPOz0Q1CDCeno__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.css" media="all" /> <style type="text/css" media="all"> /* <![CDATA[ */ #sliding-popup.sliding-popup-bottom,#sliding-popup.sliding-popup-bottom .eu-cookie-withdraw-banner,.eu-cookie-withdraw-tab{background:gray}#sliding-popup.sliding-popup-bottom.eu-cookie-withdraw-wrapper{background:transparent}#sliding-popup .popup-content #popup-text h1,#sliding-popup .popup-content #popup-text h2,#sliding-popup .popup-content #popup-text h3,#sliding-popup .popup-content #popup-text p,.eu-cookie-compliance-secondary-button,.eu-cookie-withdraw-tab{color:#fff !important}.eu-cookie-withdraw-tab{border-color:#fff}.eu-cookie-compliance-more-button{color:#fff !important} /* ]]> */ </style> <!--[if lte IE 7]> <link type="text/css" rel="stylesheet" href="https://www.biorxiv.org/sites/default/files/advagg_css/css__ElJr3PIJEvw3qLXc1cnYiLj2G4KgDPSXFOfm6Phf8hw__JdWGm15cDWjsK6KrFlQVXQix9YgNeYysf22XZHj-Y-c__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.css" media="all" /> <![endif]--> <link type="text/css" rel="stylesheet" href="https://www.biorxiv.org/sites/default/files/advagg_css/css__Wnlyen9qEpwh_Qaf9okEu4QdVGM0BDothxeqA6Nbvo8__EJmw6SZD9bYoS8jocCpPYS3JFRURpdzmuvJoAUNiI-g__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.css" media="all" /> <link type="text/css" rel="stylesheet" href="https://www.biorxiv.org/sites/default/files/advagg_css/css__AWaUjB_CJFqdCLsTWh7_WG-W7zo3fP_0gXCzZa32v_g__igagZiGB2PktJMjUpZ2u3tnc56saoUGIrD5N0KSRmI4__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.css" media="all" /> <!--[if (lt IE 9)&(!IEMobile)]> <link type="text/css" rel="stylesheet" href="https://www.biorxiv.org/sites/default/files/advagg_css/css__XH6bpcI0f2dImc-p674DLCZtWBGb-QwxJK1YexVGtno__vUceGprdo5nIhV6DH93X7fI3r8RcTJbChbas9TQXeW4__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.css" media="all" /> <![endif]--> <!--[if gte IE 9]><!--> <link type="text/css" rel="stylesheet" href="https://www.biorxiv.org/sites/default/files/advagg_css/css__2WBMox6sOrN42ss5lCnH7WWVRdFdJCxtTKnQJYRwTE4__yqNvNYLvMpjy3ffuJrjjm9uW2i-Me1c23KLYuWHaqio__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.css" media="all" /> <!--<![endif]--> <link type="text/css" rel="stylesheet" href="https://www.biorxiv.org/sites/default/files/advagg_css/css__5MZAvuGF3rUWh72Qvpop9cdPSWpqBpEVThJVpbjFJZU__5c1ZiN_pM9tjxvpyA9VpEacScF0S_W4R222pC-s_-Pk__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.css" media="all" /> <link type="text/css" rel="stylesheet" href="https://d33xdlntwy0kbs.cloudfront.net/cshl_custom.css" media="all" /> <script type="text/javascript" src="https://www.biorxiv.org/sites/default/files/advagg_js/js__BKYqkKToQ7EjirB7eIdMEH5521EU3da9IpoOs8Ex2XI__aSjVoX8giBmLhN2EbCgIGQJNu89Mh5aVu1LvI_gkJ7Y__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.js"></script> <script type="text/javascript" src="//cdn.jsdelivr.net/qtip2/2.2.1/jquery.qtip.min.js"></script> <script type="text/javascript" src="https://www.biorxiv.org/sites/default/files/advagg_js/js__4Cn2dxvNlsJ-sHe6QOTLREaQvcqb0Yh0Zm9tTOHtQow__JeZEUjzbaj_yX6UjCI8eBbXy_J64ZVuoWmc2fSpLZHo__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.js"></script> <script type="text/javascript" src="https://www.google.com/recaptcha/api.js?hl=en&render=explicit&onload=drupalRecaptchaOnload"></script> <script type="text/javascript" src="https://www.biorxiv.org/sites/default/files/advagg_js/js__dGWpV57YWu3sX6UOe04RMH-iP9jSkEP7Ajt0caYXZZk__1l8Wa0iuIek7SEVmMuU0Y9TlAvRR-XZVfl1u9ezOPes__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.js"></script> <script type="text/javascript" async="async" src="https://scholar.google.com/scholar_js/casa.js"></script> <script type="text/javascript" async="async" src="https://www.googletagmanager.com/gtag/js?id=G-RZD586MC3Q"></script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i<a.length;i++)j=a[i],e(j)?g(j,0,l,0):w(j)?B(j):Object(j)===j&&h(j,l);else Object(a)===a&&h(a,l)},B.addPrefix=function(a,b){z[a]=b},B.addFilter=function(a){x.push(a)},B.errorTimeout=1e4,null==b.readyState&&b.addEventListener&&(b.readyState="loading",b.addEventListener("DOMContentLoaded",A=function(){b.removeEventListener("DOMContentLoaded",A,0),b.readyState="complete"},0)),a.yepnope=k(),a.yepnope.executeStack=h,a.yepnope.injectJs=function(a,c,d,e,i,j){var k=b.createElement("script"),l,o,e=e||B.errorTimeout;k.src=a;for(o in d)k.setAttribute(o,d[o]);c=j?h:c||f,k.onreadystatechange=k.onload=function(){!l&&g(k.readyState)&&(l=1,c(),k.onload=k.onreadystatechange=null)},m(function(){l||(l=1,c(1))},e),i?k.onload():n.parentNode.insertBefore(k,n)},a.yepnope.injectCss=function(a,c,d,e,g,i){var e=b.createElement("link"),j,c=i?h:c||f;e.href=a,e.rel="stylesheet",e.type="text/css";for(j in d)e.setAttribute(j,d[j]);g||(n.parentNode.insertBefore(e,n),m(c,0))}})(this,document); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- yepnope({ test: Modernizr.matchmedia, nope: '/sites/all/libraries/media-match/media.match.min.js' }); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- var _prum=[['id', '612e3d94173350001100005d'], ['mark', 'firstbyte', (new Date()).getTime()]]; (function() { var s=document.getElementsByTagName('script')[0], p=document.createElement('script'); p.async='async'; p.src='//rum-static.pingdom.net/prum.min.js';s.parentNode.insertBefore(p,s);})(); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- if(typeof window.MathJax === "undefined") window.MathJax = { menuSettings: { zoom: "Click" } }; //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- window.dataLayer = window.dataLayer || [];function gtag(){dataLayer.push(arguments)};gtag("js", new Date());gtag("set", "developer_id.dMDhkMT", true);gtag("config", "G-RZD586MC3Q", {"groups":"default","anonymize_ip":true}); //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- jQuery.extend(Drupal.settings,{"basePath":"\/","pathPrefix":"","ajaxPageState":{"theme":"jcore_1","theme_token":"6wugiB-SKk46o6O8yghKwxvNGxWAkmkphF1k2fnU2D0"},"colorbox":{"opacity":"0.85","current":"{current} of {total}","previous":"\u00ab Prev","next":"Next \u00bb","close":"Close","maxWidth":"98%","maxHeight":"98%","fixed":true,"mobiledetect":true,"mobiledevicewidth":"480px"},"highwire":{"nid":"4217464","apath":"\/biorxiv\/early\/2024\/11\/12\/2024.11.12.622964.atom","pisa":"biorxiv;2024.11.12.622964v1","ac":{"\/biorxiv\/early\/2024\/11\/12\/2024.11.12.622964.atom":{"access":{"full":true},"pisa_id":"","apath":"\/biorxiv\/early\/2024\/11\/12\/2024.11.12.622964.atom","jcode":"biorxiv"}},"processed":["highwire_math"],"markup":[{"requested":"abstract","variant":"abstract","view":"abstract","pisa":"biorxiv;2024.11.12.622964v1"}],"modal_window_width":"560","share_modal_width":"560","share_modal_title":"Share this Article"},"jcarousel":{"ajaxPath":"\/jcarousel\/ajax\/views"},"instances":"{\u0022highwire_abstract_tooltip\u0022:{\u0022content\u0022:{\u0022text\u0022:\u0022\u0022},\u0022style\u0022:{\u0022tip\u0022:{\u0022width\u0022:20,\u0022height\u0022:20,\u0022border\u0022:1,\u0022offset\u0022:0,\u0022corner\u0022:true},\u0022classes\u0022:\u0022qtip-custom hw-tooltip hw-abstract-tooltip qtip-shadow qtip-rounded\u0022,\u0022classes_custom\u0022:\u0022hw-tooltip hw-abstract-tooltip\u0022},\u0022position\u0022:{\u0022at\u0022:\u0022right center\u0022,\u0022my\u0022:\u0022left center\u0022,\u0022viewport\u0022:true,\u0022adjust\u0022:{\u0022method\u0022:\u0022shift\u0022}},\u0022show\u0022:{\u0022event\u0022:\u0022mouseenter click \u0022,\u0022solo\u0022:true},\u0022hide\u0022:{\u0022event\u0022:\u0022mouseleave \u0022,\u0022fixed\u0022:1,\u0022delay\u0022:\u0022100\u0022}},\u0022highwire_author_tooltip\u0022:{\u0022content\u0022:{\u0022text\u0022:\u0022\u0022},\u0022style\u0022:{\u0022tip\u0022:{\u0022width\u0022:15,\u0022height\u0022:15,\u0022border\u0022:1,\u0022offset\u0022:0,\u0022corner\u0022:true},\u0022classes\u0022:\u0022qtip-custom hw-tooltip hw-author-tooltip qtip-shadow qtip-rounded\u0022,\u0022classes_custom\u0022:\u0022hw-tooltip hw-author-tooltip\u0022},\u0022position\u0022:{\u0022at\u0022:\u0022top center\u0022,\u0022my\u0022:\u0022bottom center\u0022,\u0022viewport\u0022:true,\u0022adjust\u0022:{\u0022method\u0022:\u0022\u0022}},\u0022show\u0022:{\u0022event\u0022:\u0022mouseenter \u0022,\u0022solo\u0022:true},\u0022hide\u0022:{\u0022event\u0022:\u0022mouseleave \u0022,\u0022fixed\u0022:1,\u0022delay\u0022:\u0022100\u0022}},\u0022highwire_reflinks_tooltip\u0022:{\u0022content\u0022:{\u0022text\u0022:\u0022\u0022},\u0022style\u0022:{\u0022tip\u0022:{\u0022width\u0022:15,\u0022height\u0022:15,\u0022border\u0022:1,\u0022mimic\u0022:\u0022top center\u0022,\u0022offset\u0022:0,\u0022corner\u0022:true},\u0022classes\u0022:\u0022qtip-custom hw-tooltip hw-ref-link-tooltip qtip-shadow qtip-rounded\u0022,\u0022classes_custom\u0022:\u0022hw-tooltip hw-ref-link-tooltip\u0022},\u0022position\u0022:{\u0022at\u0022:\u0022bottom left\u0022,\u0022my\u0022:\u0022top left\u0022,\u0022viewport\u0022:true,\u0022adjust\u0022:{\u0022method\u0022:\u0022flip\u0022}},\u0022show\u0022:{\u0022event\u0022:\u0022mouseenter \u0022,\u0022solo\u0022:true},\u0022hide\u0022:{\u0022event\u0022:\u0022mouseleave \u0022,\u0022fixed\u0022:1,\u0022delay\u0022:\u0022100\u0022}}}","qtipDebug":"{\u0022leaveElement\u0022:0}","panel_ajax_tab":{"path":"sites\/all\/modules\/contrib\/panels_ajax_tab"},"disqus":{"domain":"biorxivstage","url":"https:\/\/www.biorxiv.org\/content\/10.1101\/2024.11.12.622964v1","title":"Development of a pipeline to evaluate YAP-TEAD inhibitor potential - direct TEAD inhibition represses cancerous growth in a NF2-mutant model of mesothelioma","identifier":"node\/4217464"},"panels_ajax_pane":{"new-28877068-b9cb-4641-830b-b6b4638c98bb":"{\u0022encrypted\u0022:\u0022{\\\u0022encrypted\\\u0022:\\\u0022d2t43gf8NmrWmhEGgwrtwkgKjplyJqE06e3KfIzsWCOCwnZkZeDV99\\\\\\\/NYWxDH1u3uiQZpOpkromU4hHyTaLp3RKvrYItKNGLykPVtaE8VOKFj93TzSYnhDGnQRuuyJkmEcnzbP322sZH8sS8Gx59YdkPDQ0d+nlRoCwUp4wJyC8Jf6zJ91bpVqKr7f0Qb6Oq6YjNWcLak3qbNPQTtIVCS5A\\\\\\\/zkZ1Tcf8scxdtpdQ8VgDgcbLFRsv7NMxOg2blSUPZeIqcK7kcGAF\\\\\\\/4jr0OveQjB0\\\\\\\/C+FTqGh+S2wWW+MRFeZYaDoq1yMDu4gRIj722YKUJklft+eoJQrPXhp9W6+UqyqMrp\\\\\\\/6XmeiCRxItmep0UwHtpeAkzLZlyJ1HQ\\\\\\\/7QsdMovZqpDvBz+KeM2zBaX+UyMwtRvakNg9KYN3TI3zCqE2huzdfkoafxkkUW3YsvWvFNOTJUVQSFXcI6nHgogpQdSt+3OLI9UP+U1+6kZPrHgkxP\\\\\\\/4ZLd7SXD\\\\\\\/P9Ef+8SuvAhoa\\\\\\\/zdZtt6boJ8WhTGFZQnepRS5dFJBnB6SCRep3FOIHZD67eUvVkrvoWgEQnXGZILi2+ntZJRFv+b1rPVmEJEdboHSVqqBCYyi+PV8MHNXwV8PEjGjlSCCgX\\\\\\\/HeHTHIPvKP2HDN\\\\\\\/FQEK1Fgk3HjFePXW++7uQZH\\\\\\\/72Wm9qleF5mlXSwR0JzWFAmCckJDdCWMoDuyt2+hspJdOnyiiA1TToB00qabP4RbIVridCUJd+vEf0m\\\\\\\/e\\\\\\\/w1J3s4k4G\\\\\\\/oUtzj08CQc+4DkYASG3mjEf2EeOHBpS95qtGGU22ykNx3xyZFXhWYC8Lq45HOEjteIMhfsMiSWxp0G\\\\\\\/SqMMtq1CkCycSL9BrrwQrDWNLawqjp2bUd91\\\\\\\/6aT3gf1bjE2LYqR39SwgZGdmCrRvWgShCb4Nt53OSsVYdB5KMZamPEa3BOvFkE8Jf+b0zVQBvciDV0j8GBqIzmJ8u8ZLEEhOeleWNdhwTrKto0OKlODP7MJg3GszERY4ANesLr79nfnXJ3AFxVA87DcMBuTLDrsSwqgl8ivIvJXEcO\\\\\\\/S6QI3k9KSvdxe9jPBsUJ208k1ZIJfOVnifOyc8m7RZrd4\\\\\\\/hFIjp\\\\\\\/zvd6NCG7yfDh5tuvMfWwKOfjAK9F0nSHv33x5LQn\\\\\\\/AQbtguVEaFvlWUBa1K4HteB1axgFdrVQQFfgsrXm7+xQQ6GTP+vmq5iP2GGcyarxPAJAlpcUbU4EqZJs9jePENjssDnrCaAXrc1eM+S55c0KiNzfk7FuWYcV9dCV7ypQUindxQs4KJz2hL7cWybexTPvH6tMxf2QAkIX6aXwhOdt180ZfS8HUhXJjikNlXJU4\\\u0022,\\\u0022iv\\\u0022:\\\u0022bZ6Lb\\\\\\\/0YTsvQ7jQSOKLQ7g==\\\u0022,\\\u0022salt\\\u0022:\\\u0022f9d8845712f72c9fee5db7d9ff111eab\\\u0022}\u0022,\u0022hmac\u0022:\u002207f3102d2d2d092f151089ef1f43b0e1f9e57c4d02729be8580a312549672719\u0022}"},"urlIsAjaxTrusted":{"\/content\/10.1101\/2024.11.12.622964v1":true},"ws_fl":{"width":100,"height":21},"ws_gpo":{"size":"","annotation":"","lang":"","callback":"","width":300},"color":{"logo":"https:\/\/www.biorxiv.org\/sites\/default\/files\/biorxiv_article.jpg"},"highwire_list_expand":{"is_collapsed":"1"},"highwireResponsive":{"enquire_enabled":1,"breakpoints_configured":1,"breakpoints":{"zero":"all and (min-width: 0px)","xsmall":"all and (min-width: 380px)","narrow":"all and (min-width: 768px) and (min-device-width: 768px), (max-device-width: 800px) and (min-width: 768px) and (orientation:landscape)","normal":"all and (min-width: 980px) and (min-device-width: 980px), all and (max-device-width: 1024px) and (min-width: 1024px) and (orientation:landscape)","wide":"all and (min-width: 1220px)"}},"eu_cookie_compliance":{"popup_enabled":1,"popup_agreed_enabled":0,"popup_hide_agreed":0,"popup_clicking_confirmation":1,"popup_scrolling_confirmation":false,"popup_html_info":"\u003Cdiv\u003E\n \u003Cdiv class=\u0022popup-content info\u0022\u003E\n \u003Cdiv id=\u0022popup-text\u0022\u003E\n \u003Cp\u003EWe use cookies on this site to enhance your user experience. By clicking any link on this page you are giving your consent for us to set cookies.\u003C\/p\u003E\n \u003C\/div\u003E\n \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022Continue\u0022\n class=\u0022agree-button eu-cookie-compliance-default-button\u0022\u003EContinue\u003C\/button\u003E\n \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022Find out more\u0022\n class=\u0022find-more-button eu-cookie-compliance-more-button\u0022\u003EFind out more\u003C\/button\u003E\n \u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E","use_mobile_message":false,"mobile_popup_html_info":"\u003Cdiv\u003E\n \u003Cdiv class=\u0022popup-content info\u0022\u003E\n \u003Cdiv id=\u0022popup-text\u0022\u003E\n \u003C\/div\u003E\n \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022Continue\u0022\n class=\u0022agree-button eu-cookie-compliance-default-button\u0022\u003EContinue\u003C\/button\u003E\n \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022Find out more\u0022\n class=\u0022find-more-button eu-cookie-compliance-more-button\u0022\u003EFind out more\u003C\/button\u003E\n \u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E","mobile_breakpoint":"768","popup_html_agreed":"\u003Cdiv\u003E\n \u003Cdiv class=\u0022popup-content agreed\u0022\u003E\n \u003Cdiv id=\u0022popup-text\u0022\u003E\n \u003Ch2\u003EThank you for accepting cookies\u003C\/h2\u003E\u003Cp\u003EYou can now hide this message or find out more about cookies.\u003C\/p\u003E \u003C\/div\u003E\n \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n \u003Cbutton type=\u0022button\u0022 class=\u0022hide-popup-button eu-cookie-compliance-hide-button\u0022\u003EHide\u003C\/button\u003E\n \u003Cbutton type=\u0022button\u0022 class=\u0022find-more-button eu-cookie-compliance-more-button-thank-you\u0022 \u003EMore info\u003C\/button\u003E\n \u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E","popup_use_bare_css":false,"popup_height":"auto","popup_width":"100%","popup_delay":1000,"popup_link":"\/help\/cookie-policy","popup_link_new_window":1,"popup_position":null,"popup_language":"en","store_consent":false,"better_support_for_screen_readers":0,"reload_page":0,"domain":"","popup_eu_only_js":0,"cookie_lifetime":"365","cookie_session":false,"disagree_do_not_show_popup":0,"method":"default","whitelisted_cookies":"","withdraw_markup":"\u003Cbutton type=\u0022button\u0022 class=\u0022eu-cookie-withdraw-tab\u0022\u003EPrivacy settings\u003C\/button\u003E\n\u003Cdiv class=\u0022eu-cookie-withdraw-banner\u0022\u003E\n \u003Cdiv class=\u0022popup-content info\u0022\u003E\n \u003Cdiv id=\u0022popup-text\u0022\u003E\n \u003Cp\u003E\u0026lt;h2\u0026gt;We use cookies on this site to enhance your user experience\u0026lt;\/h2\u0026gt;\u0026lt;p\u0026gt;You have given your consent for us to set cookies.\u0026lt;\/p\u0026gt;\u003C\/p\u003E\n \u003C\/div\u003E\n \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n \u003Cbutton type=\u0022button\u0022 class=\u0022eu-cookie-withdraw-button\u0022\u003EWithdraw consent\u003C\/button\u003E\n \u003C\/div\u003E\n \u003C\/div\u003E\n\u003C\/div\u003E\n","withdraw_enabled":false},"googleanalytics":{"account":["G-RZD586MC3Q"],"trackOutbound":1,"trackMailto":1,"trackDownload":1,"trackDownloadExtensions":"7z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip","trackColorbox":1},"jnl_biorxiv_styles":{"defaultJCode":"biorxiv"},"omega":{"layouts":{"primary":"normal","order":["narrow","normal","wide"],"queries":{"narrow":"all and (min-width: 768px) and (min-device-width: 768px), (max-device-width: 800px) and (min-width: 768px) and (orientation:landscape)","normal":"all and (min-width: 980px) and (min-device-width: 980px), all and (max-device-width: 1024px) and (min-width: 1024px) and (orientation:landscape)","wide":"all and (min-width: 1220px)"}}}}); //--><!]]> </script> <!--[if lt IE 9]><script src="http://html5shiv.googlecode.com/svn/trunk/html5.js"></script><![endif]--> </head> <body class="html not-front not-logged-in page-node page-node- page-node-4217464 node-type-highwire-article context-content hw-default-jcode-biorxiv hw-article-type-article hw-article-category-new-results"> <!-- Google Tag Manager --> <noscript><iframe src="//www.googletagmanager.com/ns.html?id=GTM-M677548" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript> <script type="text/javascript">(function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-M677548');</script> <!-- End Google Tag Manager --> <div id="skip-link"> <a href="#main-content" class="element-invisible element-focusable">Skip to main content</a> </div> <div class="page clearfix page-box-shadows footer-borders panels-page panels-layout-jcore_2col" id="page"> <header id="section-header" class="section section-header"> <div id="zone-branding" class="zone zone-branding clearfix print-display-block container-30"> <div class="grid-15 prefix-1 region region-branding print-display-block" id="region-branding"> <div class="region-inner region-branding-inner"> <div class="branding-data clearfix"> <div class="logo-img"> <a href="/" rel="home" class="" data-icon-position="" data-hide-link-title="0"><img alt="bioRxiv" src="https://www.biorxiv.org/sites/default/files/biorxiv_article.jpg" /></a> </div> </div> </div> </div><div class="grid-11 suffix-1 region region-branding-second print-hidden" id="region-branding-second"> <div class="region-inner region-branding-second-inner"> <div class="block block-system block-menu block-main-menu block-system-main-menu odd block-without-title" id="block-system-main-menu"> <div class="block-inner clearfix"> <div class="content clearfix"> <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf" role="menuitem"><a href="/" title="" class="" data-icon-position="" data-hide-link-title="0">Home</a></li> <li class="leaf" role="menuitem"><a href="/about-biorxiv" class="" data-icon-position="" data-hide-link-title="0">About</a></li> <li class="leaf" role="menuitem"><a href="/submit-a-manuscript" class="" data-icon-position="" data-hide-link-title="0">Submit</a></li> <li class="last leaf" role="menuitem"><a href="/alertsrss" title="" class="" data-icon-position="" data-hide-link-title="0">ALERTS / RSS</a></li> </ul></nav> </div> </div> </div><div class="block block-panels-mini block-biorxiv-search-box block-panels-mini-biorxiv-search-box even block-without-title" id="block-panels-mini-biorxiv-search-box"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panel-1col clearfix" id="mini-panel-biorxiv_search_box"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-seach-quicksearch" > <div class="pane-content"> <form class="highwire-quicksearch button-style-mini button-style-mini" action="/content/10.1101/2024.11.12.622964v1" method="post" id="highwire-search-quicksearch-form-0" accept-charset="UTF-8"><div><div class="form-item form-item-label-invisible form-type-textfield form-item-keywords"> <label class="element-invisible" for="search_rightsidebar_keywords_1143210785">Search for this keyword </label> <input placeholder="Search" type="text" id="search_rightsidebar_keywords_1143210785" name="keywords" value="" size="60" maxlength="128" class="form-text" /> </div> <div class="button-wrapper button-mini"><span class="icon-search"></span><input data-icon-only="1" data-font-icon="icon-search" data-icon-position="after" type="submit" id="search_rightsidebar_submit_1360097465" name="op" value="Search" class="form-submit" /></div><input type="hidden" name="form_build_id" value="form-1NQ7AS0hyGvoVyucLNHhK9z0tXAmeR_bMfX_WrU38g0" /> <input type="hidden" name="form_id" value="highwire_search_quicksearch_form_0" /> </div></form> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-2 advanced-search-link" > <div class="pane-content"> <a href="/search">Advanced Search</a> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div id="zone-header" class="zone zone-header clearfix container-30"> </div> </header> <section id="section-content" class="section section-content"> <div id="zone-content" class="zone zone-content clearfix container-30"> <div class="grid-28 suffix-1 prefix-1 region region-content" id="region-content"> <div class="region-inner region-content-inner"> <a id="main-content"></a> <div class="block block-system block-main block-system-main odd block-without-title" id="block-system-main"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panels-960-layout jcore-2col-layout" > <div class="panel-row-wrapper clearfix"> <div class="main-content-wrapper grid-17 suffix-1 alpha"> <div class="panel-panel panel-region-content"> <div class="inside"><div class="panel-pane pane-highwire-article-citation" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-article node4217464" data-node-nid="4217464" id="node-4217464--22002262746" data-pisa="biorxiv;2024.11.12.622964v1" data-pisa-master="biorxiv;2024.11.12.622964" data-apath="/biorxiv/early/2024/11/12/2024.11.12.622964.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-biorxiv-article-top clearfix has-author-tooltip" > <span class="biorxiv-article-type"> New Results </span> <h1 class="highwire-cite-title" id="page-title">Development of a pipeline to evaluate YAP-TEAD inhibitor potential <em>-</em> direct TEAD inhibition represses cancerous growth in a <em>NF2</em>-mutant model of mesothelioma</h1> <div class="highwire-cite-authors" ><span class="highwire-citation-authors"><span class="highwire-citation-author first hw-author-orcid-logo-wrapper" data-delta="0"><a href="http://orcid.org/0000-0003-4127-8917" target="_blank" class="hw-author-orcid-logo link-icon-only link-icon"><span class="hw-icon-orcid hw-icon-color-orcid"></span> <span class="title element-invisible">View ORCID Profile</span></a><span class="nlm-given-names">Richard</span> <span class="nlm-surname">Cunningham</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Siyang</span> <span class="nlm-surname">Jia</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Krishna</span> <span class="nlm-surname">Purohit</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="3"><a href="http://orcid.org/0000-0003-2055-0221" target="_blank" class="hw-author-orcid-logo link-icon-only link-icon"><span class="hw-icon-orcid hw-icon-color-orcid"></span> <span class="title element-invisible">View ORCID Profile</span></a><span class="nlm-given-names">Michaela Noskova</span> <span class="nlm-surname">Fairley</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Yue</span> <span class="nlm-surname">Lin</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="5"><a href="http://orcid.org/0000-0002-5447-9569" target="_blank" class="hw-author-orcid-logo link-icon-only link-icon"><span class="hw-icon-orcid hw-icon-color-orcid"></span> <span class="title element-invisible">View ORCID Profile</span></a><span class="nlm-given-names">Ning Sze</span> <span class="nlm-surname">Hui</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="6"><a href="http://orcid.org/0000-0002-0590-4135" target="_blank" class="hw-author-orcid-logo link-icon-only link-icon"><span class="hw-icon-orcid hw-icon-color-orcid"></span> <span class="title element-invisible">View ORCID Profile</span></a><span class="nlm-given-names">Rebecca E.</span> <span class="nlm-surname">Graham</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="7"><a href="http://orcid.org/0000-0003-3173-9521" target="_blank" class="hw-author-orcid-logo link-icon-only link-icon"><span class="hw-icon-orcid hw-icon-color-orcid"></span> <span class="title element-invisible">View ORCID Profile</span></a><span class="nlm-given-names">Adriano G.</span> <span class="nlm-surname">Rossi</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Justyna</span> <span class="nlm-surname">Cholewa-Waclaw</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="9"><a href="http://orcid.org/0000-0001-5541-9747" target="_blank" class="hw-author-orcid-logo link-icon-only link-icon"><span class="hw-icon-orcid hw-icon-color-orcid"></span> <span class="title element-invisible">View ORCID Profile</span></a><span class="nlm-given-names">Neil O.</span> <span class="nlm-surname">Carragher</span></span>, <span class="highwire-citation-author hw-author-orcid-logo-wrapper" data-delta="10"><a href="http://orcid.org/0000-0003-0746-7482" target="_blank" class="hw-author-orcid-logo link-icon-only link-icon"><span class="hw-icon-orcid hw-icon-color-orcid"></span> <span class="title element-invisible">View ORCID Profile</span></a><span class="nlm-given-names">Carsten Gram</span> <span class="nlm-surname">Hansen</span></span></span></div> <div class="highwire-cite-metadata" ><span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">doi:</span> https://doi.org/10.1101/2024.11.12.622964 </span></div> </div> <div id="hw-article-author-popups-node-4217464--22002262746" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Richard Cunningham </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span><span class='nlm-institution'>University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair</span>, Edinburgh bioQuarter, 5 Little <span class='nlm-country'>France</span> Drive, Edinburgh EH16 4UU, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Richard%2BCunningham%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Cunningham%20R&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ARichard%2BCunningham%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-4127-8917" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Richard Cunningham</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Siyang Jia </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span><span class='nlm-institution'>University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair</span>, Edinburgh bioQuarter, 5 Little <span class='nlm-country'>France</span> Drive, Edinburgh EH16 4UU, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Siyang%2BJia%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Jia%20S&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ASiyang%2BJia%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">Krishna Purohit </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span><span class='nlm-institution'>University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair</span>, Edinburgh bioQuarter, 5 Little <span class='nlm-country'>France</span> Drive, Edinburgh EH16 4UU, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Krishna%2BPurohit%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Purohit%20K&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AKrishna%2BPurohit%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">Michaela Noskova Fairley </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span><span class='nlm-institution'>University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair</span>, Edinburgh bioQuarter, 5 Little <span class='nlm-country'>France</span> Drive, Edinburgh EH16 4UU, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Michaela%2BNoskova%2BFairley%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Fairley%20MN&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AMichaela%2BNoskova%2BFairley%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-2055-0221" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Michaela Noskova Fairley</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">Yue Lin </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span><span class='nlm-institution'>University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair</span>, Edinburgh bioQuarter, 5 Little <span class='nlm-country'>France</span> Drive, Edinburgh EH16 4UU, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yue%2BLin%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Lin%20Y&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AYue%2BLin%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">Ning Sze Hui </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span><span class='nlm-institution'>University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair</span>, Edinburgh bioQuarter, 5 Little <span class='nlm-country'>France</span> Drive, Edinburgh EH16 4UU, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ning%2BSze%2BHui%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Hui%20NS&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ANing%2BSze%2BHui%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-5447-9569" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Ning Sze Hui</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">Rebecca E. Graham </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>3</span><span class='nlm-institution'>Centre for Clinical Brain Sciences, Anne Rowling Regenerative Neurology Clinic, University of Edinburgh</span>, Edinburgh, EH16 4SB, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Rebecca%2BE.%2BGraham%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Graham%20RE&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ARebecca%2BE.%2BGraham%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0002-0590-4135" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Rebecca E. Graham</a></li></ul></div><div class="author-tooltip-7"><div class="author-tooltip-name">Adriano G. Rossi </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span><span class='nlm-institution'>University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair</span>, Edinburgh bioQuarter, 5 Little <span class='nlm-country'>France</span> Drive, Edinburgh EH16 4UU, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Adriano%2BG.%2BRossi%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Rossi%20AG&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AAdriano%2BG.%2BRossi%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0003-3173-9521" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Adriano G. Rossi</a></li></ul></div><div class="author-tooltip-8"><div class="author-tooltip-name">Justyna Cholewa-Waclaw </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>2</span><span class='nlm-institution'>High Content Screening Facility, Institute for Regeneration and Repair, The University of Edinburgh</span>, Edinburgh, EH16 4UU, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Justyna%2BCholewa-Waclaw%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Cholewa-Waclaw%20J&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AJustyna%2BCholewa-Waclaw%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-9"><div class="author-tooltip-name">Neil O. Carragher </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>4</span><span class='nlm-institution'>Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh</span>, Edinburgh, EH4 2XR, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Neil%2BO.%2BCarragher%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Carragher%20NO&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ANeil%2BO.%2BCarragher%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="http://orcid.org/0000-0001-5541-9747" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Neil O. Carragher</a></li></ul></div><div class="author-tooltip-10"><div class="author-tooltip-name">Carsten Gram Hansen </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span><span class='nlm-institution'>University of Edinburgh, Centre for Inflammation Research, Institute for Regeneration and Repair</span>, Edinburgh bioQuarter, 5 Little <span class='nlm-country'>France</span> Drive, Edinburgh EH16 4UU, <span class='nlm-country'>UK</span></div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Carsten%2BGram%2BHansen%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Hansen%20CG&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ACarsten%2BGram%2BHansen%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link"><a href="http://orcid.org/0000-0003-0746-7482" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Carsten Gram Hansen</a></li><li class="author-corresp-email-link last"><span>For correspondence: <a href="mailto:carsten.g.hansen@ed.ac.uk" class="" data-icon-position="" data-hide-link-title="0">carsten.g.hansen@ed.ac.uk</a></span></li></ul></div></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-panel-tabs pane-panels-ajax-tab-tabs" > <div class="pane-content"> <div class="item-list"><ul class="tabs inline panels-ajax-tab"><li class="first"><a href="/content/10.1101/2024.11.12.622964v1" class="panels-ajax-tab-tab" data-panel-name="biorxiv_tab_art" data-target-id="highwire_article_tabs" data-entity-context="node:4217464" data-trigger="" data-url-enabled="1">Abstract</a><a href="/panels_ajax_tab/biorxiv_tab_art/node:4217464/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/10.1101/2024.11.12.622964v1.full-text" class="panels-ajax-tab-tab" data-panel-name="article_tab_full_text" data-target-id="highwire_article_tabs" data-entity-context="node:4217464" data-trigger="full-text" data-url-enabled="1">Full Text</a><a href="/panels_ajax_tab/article_tab_full_text/node:4217464/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/10.1101/2024.11.12.622964v1.article-info" class="panels-ajax-tab-tab" data-panel-name="biorxiv_tab_info" data-target-id="highwire_article_tabs" data-entity-context="node:4217464" data-trigger="article-info" data-url-enabled="1">Info/History</a><a href="/panels_ajax_tab/biorxiv_tab_info/node:4217464/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/10.1101/2024.11.12.622964v1.article-metrics" class="panels-ajax-tab-tab" data-panel-name="article_tab_metrics" data-target-id="highwire_article_tabs" data-entity-context="node:4217464" data-trigger="article-metrics" data-url-enabled="1">Metrics</a><a href="/panels_ajax_tab/article_tab_metrics/node:4217464/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li class="last"><a href="/content/10.1101/2024.11.12.622964v1.full.pdf+html" class="panels-ajax-tab-tab" data-panel-name="biorxiv_tab_pdf" data-target-id="highwire_article_tabs" data-entity-context="node:4217464" data-trigger="full.pdf+html" data-url-enabled="1"><i class="icon-file-alt"></i> Preview PDF</a><a href="/panels_ajax_tab/biorxiv_tab_pdf/node:4217464/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li></ul></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-panel-tabs-container" > <div class="pane-content"> <div data-panels-ajax-tab-preloaded="biorxiv_tab_art" id="panels-ajax-tab-container-highwire_article_tabs" class="panels-ajax-tab-container"><div class="panels-ajax-tab-loading" style ="display:none"><img class="loading" src="https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif" alt="Loading" title="Loading" /></div><div class="panels-ajax-tab-wrap-biorxiv_tab_art"><div class="panel-display panel-1col clearfix" > <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-markup" > <div class="pane-content"> <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2 class="">ABSTRACT</h2><p id="p-2">As the core, tumorigenic downstream effectors of the Hippo signalling pathway, YAP/TAZ and the TEAD family of transcription factors represent attractive targets for drug discovery efforts within cancer research. This is particularly true within the context of pleural mesothelioma, in which there are many recent preclinical developments and clinical trials evaluating the efficacy of TEAD inhibitors. The range of inhibitors have shown great promise, but comparisons of their performances are so far limited. Here we develop a high content pipeline that enables a comparative analysis of currently developed YAP/TAZ-TEAD inhibitors. We take advantage of isogenic cellular models that enable us to examine inhibitor specificity. We identify genetic compensation of the Hippo pathway transcriptional module, with implications for therapeutic targeting, and implement Cell Painting to develop a detailed morphological profiling pipeline that enables further characterisation, quantification, and analysis of off-target effects. Our pipeline is scalable and allows us to establish specificity and comparative potency within cancer relevant assays in a clinically relevant cellular model.</p></div><h3>Competing Interest Statement</h3><p id="p-3">The authors have declared no competing interest.</p><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-biorxiv-copyright" > <div class="pane-content"> <div class="field field-name-field-highwire-copyright field-type-text field-label-inline clearfix"><div class="field-label">Copyright </div><div class="field-items"><div class="field-item even">The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.<span class="license-type"> It is made available under a <a href="http://creativecommons.org/licenses/by/4.0/" class="" data-icon-position="" data-hide-link-title="0">CC-BY 4.0 International license</a>.</span></div></div></div> </div> </div> </div> </div> </div> </div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-disqus-comment" > <div class="pane-content"> <div id="disqus_thread"><noscript><p><a href="http://biorxivstage.disqus.com/?url=https%3A%2F%2Fwww.biorxiv.org%2Fcontent%2F10.1101%2F2024.11.12.622964v1" class="" data-icon-position="" data-hide-link-title="0">View the discussion thread.</a></p></noscript></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-back-to-top" > <div class="pane-content"> <a href="#page" class="back-to-top" data-icon-position="" data-hide-link-title="0"><span class="icon-chevron-up"></span> Back to top</a> </div> </div> </div> </div> </div> <div class="sidebar-right-wrapper grid-10 omega"> <div class="panel-panel panel-region-sidebar-right"> <div class="inside"><div class="panel-pane pane-highwire-node-pager" > <div class="pane-content"> <div class="pager highwire-pager pager-mini clearfix highwire-node-pager highwire-article-pager"><span class="pager-prev"><a href="/content/10.1101/2024.11.06.622223v2" title="Correction of RBFOX1 deficit rescues Huntington’s disease mis-splicing and pathology" rel="prev" class="pager-link-prev link-icon"><span class="icon-circle-arrow-left"></span> <span class="title">Previous</span></a></span><span class="pager-next"><a href="/content/10.1101/2024.11.12.623230v1" title="Investigating the genetic relationship of Trichosporon asahii isolates using a newly developed microsatellite typing assay" rel="next" class="pager-link-next link-icon-right link-icon"><span class="title">Next</span> <span class="icon-circle-arrow-right"></span></a></span></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-custom pane-1" > <div class="pane-content"> Posted November 12, 2024. </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-biorxiv-art-tools" > <div class="pane-content"> <div id="mini-panel-biorxiv_art_tools" class="highwire-2col-stacked panel-display"> <div class="panel-row-wrapper clearfix"> <div class="content-left-wrapper content-column"> <div class="panel-panel panel-region-content-left"> <div class="inside"><div class="panel-pane pane-highwire-variant-link" > <div class="pane-content"> <a href="/content/10.1101/2024.11.12.622964v1.full.pdf" target="_self" class="article-dl-pdf-link link-icon"><span class="icon-external-link-sign"></span> <span class="title">Download PDF</span></a> </div> </div> </div> </div> </div> <div class="content-right-wrapper content-column"> <div class="panel-panel panel-region-content-right"> <div class="inside"><div class="panel-pane pane-minipanel-dialog-link pane-biorxiv-art-email" > <div class="pane-content"> <div class='minipanel-dialog-wrapper'><div class='minipanel-dialog-link-link'><a href="/" oncontextmenu="javascript: return false;" class="minipanel-dialog-link-trigger" title="Email this Article" data-icon-position="" data-hide-link-title="0"><i class = 'icon-envelope'></i> Email</a></div><div class='minipanel-dialog-link-mini' style='display:none'><div class="panel-display panel-1col clearfix" id="mini-panel-biorxiv_art_email"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-block pane-forward-form pane-forward" > <div class="pane-content"> <form action="/content/10.1101/2024.11.12.622964v1" method="post" id="forward-form" accept-charset="UTF-8"><div><div id="edit-instructions" class="form-item form-item-label-before form-type-item"> <p>Thank you for your interest in spreading the word about bioRxiv.</p><p>NOTE: Your email address is requested solely to identify you as the sender of this article.</p> </div> <div class="form-item form-item-label-before form-type-textfield form-item-email"> <label for="edit-email">Your Email <span class="form-required" title="This field is required.">*</span></label> <input type="text" id="edit-email" name="email" value="" size="58" maxlength="256" class="form-text required" /> </div> <div class="form-item form-item-label-before form-type-textfield form-item-name"> <label for="edit-name">Your Name <span class="form-required" title="This field is required.">*</span></label> <input type="text" id="edit-name" name="name" value="" size="58" maxlength="256" class="form-text required" /> </div> <div class="form-item form-item-label-before form-type-textarea form-item-recipients"> <label for="edit-recipients">Send To <span class="form-required" title="This field is required.">*</span></label> <div class="form-textarea-wrapper resizable"><textarea id="edit-recipients" name="recipients" cols="50" rows="5" class="form-textarea required"></textarea></div> <div class="description">Enter multiple addresses on separate lines or separate them with commas.</div> </div> <div id="edit-page" class="form-item form-item-label-before form-type-item"> <label for="edit-page">You are going to email the following </label> <a href="/content/10.1101/2024.11.12.622964v1" class="active" data-icon-position="" data-hide-link-title="0">Development of a pipeline to evaluate YAP-TEAD inhibitor potential - direct TEAD inhibition represses cancerous growth in a NF2-mutant model of mesothelioma</a> </div> <div id="edit-subject" class="form-item form-item-label-before form-type-item"> <label for="edit-subject">Message Subject </label> (Your Name) has forwarded a page to you from bioRxiv </div> <div id="edit-body" class="form-item form-item-label-before form-type-item"> <label for="edit-body">Message Body </label> (Your Name) thought you would like to see this page from the bioRxiv website. </div> <div class="form-item form-item-label-before form-type-textarea form-item-message"> <label for="edit-message--2">Your Personal Message </label> <div class="form-textarea-wrapper resizable"><textarea id="edit-message--2" name="message" cols="50" rows="10" class="form-textarea"></textarea></div> </div> <input type="hidden" name="path" value="node/4217464" /> <input type="hidden" name="path_cid" value="" /> <input type="hidden" name="forward_footer" value=" " /> <input type="hidden" name="form_build_id" value="form-H7mjTQHBeZ6mzYUZFgoQ2XfEQZG1vmrRjjHV9_k0ajc" /> <input type="hidden" name="form_id" value="forward_form" /> <fieldset class="captcha form-wrapper"><legend><span class="fieldset-legend">CAPTCHA</span></legend><div class="fieldset-wrapper"><div class="fieldset-description">This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.</div><input type="hidden" name="captcha_sid" value="838718494" /> <input type="hidden" name="captcha_token" value="7202dd9be1aa87d3b01e1e98811c05dc" /> <input type="hidden" name="captcha_response" value="Google no captcha" /> <div class="g-recaptcha" data-sitekey="6LfnJVIUAAAAAE-bUOMg0MJGki4lqSvDmhJp19fN" data-theme="light" data-type="image"></div></div></fieldset> <div class="form-actions form-wrapper" id="edit-actions"><input type="submit" id="edit-submit" name="op" value="Send Message" class="form-submit" /></div></div></form> </div> </div> </div> </div> </div> </div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-share-link highwire_clipboard_link_ajax" id="shareit"> <div class="pane-content"> <a href="/" class="link-icon"><span class="icon-share-alt"></span> <span class="title">Share</span></a> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-biorxiv-share highwire_clipboard_form_ajax_shareit" > <div class="pane-content"> <div class="panel-display omega-12-onecol" id="mini-panel-biorxiv_share"> <div class="panel-panel grid-12 panel-region-preface"> <div class="inside"><div class="panel-pane pane-highwire-article-citation" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-article node4217464--3" data-node-nid="4217464" id="node-4217464--41152716906" data-pisa="biorxiv;2024.11.12.622964v1" data-pisa-master="biorxiv;2024.11.12.622964" data-seqnum="4217464" data-apath="/biorxiv/early/2024/11/12/2024.11.12.622964.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-biorxiv-article-pap-list clearfix" > <div class="highwire-cite-title" > <div class="highwire-cite-title">Development of a pipeline to evaluate YAP-TEAD inhibitor potential <em>-</em> direct TEAD inhibition represses cancerous growth in a <em>NF2</em>-mutant model of mesothelioma</div> </div> <div class="highwire-cite-authors" ><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Richard</span> <span class="nlm-surname">Cunningham</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Siyang</span> <span class="nlm-surname">Jia</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Krishna</span> <span class="nlm-surname">Purohit</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Michaela Noskova</span> <span class="nlm-surname">Fairley</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Yue</span> <span class="nlm-surname">Lin</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Ning Sze</span> <span class="nlm-surname">Hui</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Rebecca E.</span> <span class="nlm-surname">Graham</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Adriano G.</span> <span class="nlm-surname">Rossi</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Justyna</span> <span class="nlm-surname">Cholewa-Waclaw</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Neil O.</span> <span class="nlm-surname">Carragher</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">Carsten Gram</span> <span class="nlm-surname">Hansen</span></span></span></div> <div class="highwire-cite-metadata" ><span class="highwire-cite-metadata-journal highwire-cite-metadata">bioRxiv </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">2024.11.12.622964; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="doi_label">doi:</span> https://doi.org/10.1101/2024.11.12.622964 </span></div> </div> </div> </div> </div> </div> </div> <div class="panel-panel grid-12 panel-region-content"> <div class="inside"><div class="panel-pane pane-highwire-article-clipboard-copy" > <div class="pane-content"> <div class = "clipboard-copy"> <span class="label-url"> <label for="dynamic">Share This Article:</label> </span> <span class="input-text-url"> <input type="text" id="dynamic" value="https://www.biorxiv.org/content/10.1101/2024.11.12.622964v1" size="50"/> </span> <span class="copy-button button"> <button id="copy-dynamic" class="clipboardjs-button" data-clipboard-target="#dynamic" data-clipboard-alert-style="tooltip" data-clipboard-alert-text="Copied!">Copy</button> </span> </div> </div> </div> </div> </div> <div class="panel-panel grid-12 panel-region-postscript"> <div class="inside"><div class="panel-pane pane-service-links text-center" > <div class="pane-content"> <div class="service-links"><a href="http://twitter.com/share?url=https%3A//www.biorxiv.org/content/10.1101/2024.11.12.622964v1&text=Development%20of%20a%20pipeline%20to%20evaluate%20YAP-TEAD%20inhibitor%20potential%20-%20direct%20TEAD%20inhibition%20represses%20cancerous%20growth%20in%20a%20NF2-mutant%20model%20of%20mesothelioma" id="twitter" title="Share this on Twitter" class="service-links-twitter" rel="nofollow" data-icon-position="" data-hide-link-title="0"><img src="https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/twitter.png" alt="Twitter logo" /></a> <a href="http://www.facebook.com/sharer.php?u=https%3A//www.biorxiv.org/content/10.1101/2024.11.12.622964v1&t=Development%20of%20a%20pipeline%20to%20evaluate%20YAP-TEAD%20inhibitor%20potential%20-%20direct%20TEAD%20inhibition%20represses%20cancerous%20growth%20in%20a%20NF2-mutant%20model%20of%20mesothelioma" id="facebook" title="Share on Facebook" class="service-links-facebook" rel="nofollow" data-icon-position="" data-hide-link-title="0"><img src="https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/fb-blue.png" alt="Facebook logo" /></a> <a href="http://www.linkedin.com/shareArticle?mini=true&url=https%3A//www.biorxiv.org/content/10.1101/2024.11.12.622964v1&title=Development%20of%20a%20pipeline%20to%20evaluate%20YAP-TEAD%20inhibitor%20potential%20-%20direct%20TEAD%20inhibition%20represses%20cancerous%20growth%20in%20a%20NF2-mutant%20model%20of%20mesothelioma&summary=&source=bioRxiv" id="linkedin" title="Publish this post to LinkedIn" class="service-links-linkedin" rel="nofollow" data-icon-position="" data-hide-link-title="0"><img src="https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/linkedin-32px.png" alt="LinkedIn logo" /></a> <a href="http://www.mendeley.com/import/?url=https%3A//www.biorxiv.org/content/10.1101/2024.11.12.622964v1&title=Development%20of%20a%20pipeline%20to%20evaluate%20YAP-TEAD%20inhibitor%20potential%20-%20direct%20TEAD%20inhibition%20represses%20cancerous%20growth%20in%20a%20NF2-mutant%20model%20of%20mesothelioma" id="mendeley" title="Share on Mendeley" class="service-links-mendeley" rel="nofollow" data-icon-position="" data-hide-link-title="0"><img src="https://www.biorxiv.org/sites/all/modules/highwire/highwire/images/mendeley.png" alt="Mendeley logo" /></a></div> </div> </div> </div> </div> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-minipanel-dialog-link pane-biorxiv-cite-tool" > <div class="pane-content"> <div class='minipanel-dialog-wrapper'><div class='minipanel-dialog-link-link'><a href="/" oncontextmenu="javascript: return false;" class="minipanel-dialog-link-trigger link-icon" title="Citation Tools"><span class="icon-globe"></span> <span class="title">Citation Tools</span></a></div><div class='minipanel-dialog-link-mini' style='display:none'><div class="panel-display panel-1col clearfix" id="mini-panel-biorxiv_cite_tool"> <div class="panel-panel panel-col"> <div><div class="panel-pane pane-highwire-citation-export" > <div class="pane-content"> <div class="highwire-citation-export"> <div class="highwire-citation-info"> <div class="highwire-article-citation highwire-citation-type-highwire-article cite-tool-node4217464--5" data-node-nid="4217464" id="citation-node-4217464--61333925116" data-pisa="biorxiv;2024.11.12.622964v1" data-pisa-master="biorxiv;2024.11.12.622964" data-seqnum="4217464" data-apath="/biorxiv/early/2024/11/12/2024.11.12.622964.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-biorxiv-article-pap-list clearfix" > <div class="highwire-cite-title" > <div class="highwire-cite-title">Development of a pipeline to evaluate YAP-TEAD inhibitor potential <em>-</em> direct TEAD inhibition represses cancerous growth in a <em>NF2</em>-mutant model of mesothelioma</div> </div> <div class="highwire-cite-authors" ><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Richard</span> <span class="nlm-surname">Cunningham</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Siyang</span> <span class="nlm-surname">Jia</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Krishna</span> <span class="nlm-surname">Purohit</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Michaela Noskova</span> <span class="nlm-surname">Fairley</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Yue</span> <span class="nlm-surname">Lin</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Ning Sze</span> <span class="nlm-surname">Hui</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Rebecca E.</span> <span class="nlm-surname">Graham</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Adriano G.</span> <span class="nlm-surname">Rossi</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Justyna</span> <span class="nlm-surname">Cholewa-Waclaw</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Neil O.</span> <span class="nlm-surname">Carragher</span></span>, <span class="highwire-citation-author" data-delta="10"><span class="nlm-given-names">Carsten Gram</span> <span class="nlm-surname">Hansen</span></span></span></div> <div class="highwire-cite-metadata" ><span class="highwire-cite-metadata-journal highwire-cite-metadata">bioRxiv </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">2024.11.12.622964; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="doi_label">doi:</span> https://doi.org/10.1101/2024.11.12.622964 </span></div> </div> </div> </div> <div class="highwire-citation-formats"> <h2>Citation Manager Formats</h2> <div class="highwire-citation-formats-links"> <span class="Z3988" title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.spage&rft.epage&rft.atitle=Development%20of%20a%20pipeline%20to%20evaluate%20YAP-TEAD%20inhibitor%20potential%20-%20direct%20TEAD%20inhibition%20represses%20cancerous%20growth%20in%20a%20NF2-mutant%20model%20of%20mesothelioma&rft.volume&rft.issue&rft.date=2024-01-01%2000%3A00%3A00&rft.stitle&rft.jtitle=bioRxiv&rft.au=Cunningham%2C+Richard&rft.au=Jia%2C+Siyang&rft.au=Purohit%2C+Krishna&rft.au=Fairley%2C+Michaela+Noskova&rft.au=Lin%2C+Yue&rft.au=Hui%2C+Ning+Sze&rft.au=Graham%2C+Rebecca+E.&rft.au=Rossi%2C+Adriano+G.&rft.au=Cholewa-Waclaw%2C+Justyna&rft.au=Carragher%2C+Neil+O.&rft.au=Hansen%2C+Carsten+Gram"></span><ul class="hw-citation-links inline button button-alt button-grid clearfix"><li class="bibtext first"><a href="/highwire/citation/4217464/bibtext" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">BibTeX</a></li><li class="bookends"><a href="/highwire/citation/4217464/bookends" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Bookends</a></li><li class="easybib"><a href="/highwire/citation/4217464/easybib" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">EasyBib</a></li><li class="endnote-tagged"><a href="/highwire/citation/4217464/endnote-tagged" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">EndNote (tagged)</a></li><li class="endnote-8-xml"><a href="/highwire/citation/4217464/endnote-8-xml" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">EndNote 8 (xml)</a></li><li class="medlars"><a href="/highwire/citation/4217464/medlars" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Medlars</a></li><li class="mendeley"><a href="/highwire/citation/4217464/mendeley" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Mendeley</a></li><li class="papers"><a href="/highwire/citation/4217464/papers" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Papers</a></li><li class="refworks-tagged"><a href="/highwire/citation/4217464/refworks-tagged" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">RefWorks Tagged</a></li><li class="reference-manager"><a href="/highwire/citation/4217464/reference-manager" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Ref Manager</a></li><li class="ris"><a href="/highwire/citation/4217464/ris" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">RIS</a></li><li class="zotero last"><a href="/highwire/citation/4217464/zotero" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Zotero</a></li></ul> </div> </div> </div> </div> </div> </div> </div> </div> </div></div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-service-links" > <div class="pane-content"> <div class="service-links"><div class="item-list"><ul><li class="first"><a href="http://twitter.com/share?url=https%3A//www.biorxiv.org/content/10.1101/2024.11.12.622964v1&count=horizontal&via=&text=Development%20of%20a%20pipeline%20to%20evaluate%20YAP-TEAD%20inhibitor%20potential%20-%20direct%20TEAD%20inhibition%20represses%20cancerous%20growth%20in%20a%20NF2-mutant%20model%20of%20mesothelioma&counturl=https%3A//www.biorxiv.org/content/10.1101/2024.11.12.622964v1" class="twitter-share-button service-links-twitter-widget" id="twitter_widget" title="Tweet This" rel="nofollow" data-icon-position="" data-hide-link-title="0"><span class="element-invisible">Tweet Widget</span></a></li><li><a href="http://www.facebook.com/plugins/like.php?href=https%3A//www.biorxiv.org/content/10.1101/2024.11.12.622964v1&layout=button_count&show_faces=false&action=like&colorscheme=light&width=100&height=21&font=&locale=" id="facebook_like" title="I Like it" class="service-links-facebook-like" rel="nofollow" data-icon-position="" data-hide-link-title="0"><span class="element-invisible">Facebook Like</span></a></li><li class="last"><a href="https://www.biorxiv.org/content/10.1101/2024.11.12.622964v1" id="google_plus_one" title="Plus it" class="service-links-google-plus-one" rel="nofollow" data-icon-position="" data-hide-link-title="0"><span class="element-invisible">Google Plus One</span></a></li></ul></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-article-collections" > <h2 class="pane-title">Subject Area</h2> <div class="pane-content"> <div class="highwire-list-wrapper highwire-article-collections"><div class="highwire-list"><ul class="highwire-article-collection-term-list"><li class="first last odd"><span class="highwire-article-collection-term"><a href="/collection/cancer-biology" class="highlight" data-icon-position="" data-hide-link-title="0">Cancer Biology<i class="icon-caret-right"></i> </a></span></li></ul></div></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-biorxiv-subject-collections block-style-col2" > <div class="pane-content"> <div class="panel-flexible panels-flexible-new clearfix" id="mini-panel-biorxiv_subject_collections"> <div class="panel-flexible-inside panels-flexible-new-inside"> <div class="panels-flexible-region panels-flexible-region-new-center panels-flexible-region-first panels-flexible-region-last"> <div class="inside panels-flexible-region-inside panels-flexible-region-new-center-inside panels-flexible-region-inside-first panels-flexible-region-inside-last"> <div class="panel-pane pane-snippet" > <div class="pane-content"> <div class="snippet biorxiv-subject-areas-table-title" id="biorxiv-subject-areas-table-title"> <div class="snippet-content"> <b>Subject Areas</b> </div> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-snippet" > <div class="pane-content"> <div class="snippet biorxiv-subject-areas-view-papers" id="biorxiv-subject-areas-view-papers"> <div class="snippet-content"> <a href="/content/early/recent"><strong>All Articles</strong></a> </div> </div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-highwire-subject-collections" > <div class="pane-content"> <ul id="collection" class="collection highwire-list-expand"><li class="outer collection depth-2 child first"><div class = "data-wrapper"><a href="/collection/animal-behavior-and-cognition" class="" data-icon-position="" data-hide-link-title="0">Animal Behavior and Cognition</a> <span class = "article-count">(5842)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/biochemistry" class="" data-icon-position="" data-hide-link-title="0">Biochemistry</a> <span class = "article-count">(13243)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/bioengineering" class="" data-icon-position="" data-hide-link-title="0">Bioengineering</a> <span class = "article-count">(10085)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/bioinformatics" class="" data-icon-position="" data-hide-link-title="0">Bioinformatics</a> <span class = "article-count">(32325)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/biophysics" class="" data-icon-position="" data-hide-link-title="0">Biophysics</a> <span class = "article-count">(16624)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/cancer-biology" class="" data-icon-position="" data-hide-link-title="0">Cancer Biology</a> <span class = "article-count">(13703)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/cell-biology" class="" data-icon-position="" data-hide-link-title="0">Cell Biology</a> <span class = "article-count">(19485)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/clinical-trials" class="" data-icon-position="" data-hide-link-title="0">Clinical Trials</a> <span class = "article-count">(138)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/developmental-biology" class="" data-icon-position="" data-hide-link-title="0">Developmental Biology</a> <span class = "article-count">(10532)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/ecology" class="" data-icon-position="" data-hide-link-title="0">Ecology</a> <span class = "article-count">(15615)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/epidemiology" class="" data-icon-position="" data-hide-link-title="0">Epidemiology</a> <span class = "article-count">(2067)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/evolutionary-biology" class="" data-icon-position="" data-hide-link-title="0">Evolutionary Biology</a> <span class = "article-count">(19921)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/genetics" class="" data-icon-position="" data-hide-link-title="0">Genetics</a> <span class = "article-count">(13164)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/genomics" class="" data-icon-position="" data-hide-link-title="0">Genomics</a> <span class = "article-count">(18231)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/immunology" class="" data-icon-position="" data-hide-link-title="0">Immunology</a> <span class = "article-count">(13344)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/microbiology" class="" data-icon-position="" data-hide-link-title="0">Microbiology</a> <span class = "article-count">(31241)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/molecular-biology" class="" data-icon-position="" data-hide-link-title="0">Molecular Biology</a> <span class = "article-count">(13013)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/neuroscience" class="" data-icon-position="" data-hide-link-title="0">Neuroscience</a> <span class = "article-count">(68156)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/paleontology" class="" data-icon-position="" data-hide-link-title="0">Paleontology</a> <span class = "article-count">(501)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/pathology" class="" data-icon-position="" data-hide-link-title="0">Pathology</a> <span class = "article-count">(2103)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/pharmacology-and-toxicology" class="" data-icon-position="" data-hide-link-title="0">Pharmacology and Toxicology</a> <span class = "article-count">(3640)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/physiology" class="" data-icon-position="" data-hide-link-title="0">Physiology</a> <span class = "article-count">(5680)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/plant-biology" class="" data-icon-position="" data-hide-link-title="0">Plant Biology</a> <span class = "article-count">(11682)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/scientific-communication-and-education" class="" data-icon-position="" data-hide-link-title="0">Scientific Communication and Education</a> <span class = "article-count">(1780)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/synthetic-biology" class="" data-icon-position="" data-hide-link-title="0">Synthetic Biology</a> <span class = "article-count">(3272)</span></div></li> <li class="outer collection depth-2 child"><div class = "data-wrapper"><a href="/collection/systems-biology" class="" data-icon-position="" data-hide-link-title="0">Systems Biology</a> <span class = "article-count">(7975)</span></div></li> <li class="outer collection depth-2 child last"><div class = "data-wrapper"><a href="/collection/zoology" class="" data-icon-position="" data-hide-link-title="0">Zoology</a> <span class = "article-count">(1800)</span></div></li> </ul> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <!-- /.panel-row-wrapper --> </div> </div> </div> </div> </div> </div> </div> </section> </div> <div class="region region-page-bottom" id="region-page-bottom"> <div class="region-inner region-page-bottom-inner"> </div> </div><script type="text/javascript" src="https://www.biorxiv.org/sites/default/files/advagg_js/js__Vh5BcRYb6VtLoN3uam6O4DIKltYUVMjVDWtakoysPq0__Wed8jsPTirEozek7dWSCS8970Cp7a9xKKgFk6FPuSVM__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.js"></script> <script type="text/javascript" src="//d33xdlntwy0kbs.cloudfront.net/cshl_custom.js"></script> <script type="text/javascript" src="https://www.biorxiv.org/sites/default/files/advagg_js/js__BmqjBnkz3MgYCAoc25s1lDRMEjLhC3mEPVonUFIHi08__Unwv5-ZIuHBfFwytsjEx1niBVJ7n1T4lPws7VrkHXM4__EJK5Ll7b5lGK3vCcC61vJSpnnlwWCn8d6_LJW7hCX3M.js"></script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- function euCookieComplianceLoadScripts() {} //--><!]]> </script> <script type="text/javascript"> <!--//--><![CDATA[//><!-- var eu_cookie_compliance_cookie_name = ""; //--><!]]> </script> </body> </html>