Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing Library
The transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are the major downstream effectors in the Hippo pathway and are involved in cancer progression through modulation of the activity of TEAD (transcriptional enhanced associate doma...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/391 |
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| author | Angela Lauriola Elisa Uliassi Matteo Santucci Maria Laura Bolognesi Marco Mor Laura Scalvini Gian Marco Elisi Gaia Gozzi Lorenzo Tagliazucchi Gaetano Marverti Stefania Ferrari Lorena Losi Domenico D’Arca Maria Paola Costi |
| author_facet | Angela Lauriola Elisa Uliassi Matteo Santucci Maria Laura Bolognesi Marco Mor Laura Scalvini Gian Marco Elisi Gaia Gozzi Lorenzo Tagliazucchi Gaetano Marverti Stefania Ferrari Lorena Losi Domenico D’Arca Maria Paola Costi |
| author_sort | Angela Lauriola |
| collection | DOAJ |
| description | The transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are the major downstream effectors in the Hippo pathway and are involved in cancer progression through modulation of the activity of TEAD (transcriptional enhanced associate domain) transcription factors. To exploit the advantages of drug repurposing in the search of new drugs, we developed a similar approach for the identification of new hits interfering with TEAD target gene expression. In our study, a 27-member in-house library was assembled, characterized, and screened for its cancer cell growth inhibition effect. In a secondary luciferase-based assay, only seven compounds confirmed their specific involvement in TEAD activity. <b>IA5</b> bearing a p-quinoid structure reduced the cytoplasmic level of phosphorylated YAP and the YAP–TEAD complex transcriptional activity and reduced cancer cell growth. <b>IA5</b> is a promising hit compound for TEAD activity modulator development. |
| first_indexed | 2024-03-09T21:13:59Z |
| format | Article |
| id | doaj.art-6b37af2ad3704c51b856208309d6c8c9 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:13:59Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6b37af2ad3704c51b856208309d6c8c92023-11-23T21:38:36ZengMDPI AGPharmaceutics1999-49232022-02-0114239110.3390/pharmaceutics14020391Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing LibraryAngela Lauriola0Elisa Uliassi1Matteo Santucci2Maria Laura Bolognesi3Marco Mor4Laura Scalvini5Gian Marco Elisi6Gaia Gozzi7Lorenzo Tagliazucchi8Gaetano Marverti9Stefania Ferrari10Lorena Losi11Domenico D’Arca12Maria Paola Costi13Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Via Belmeloro 6, 40126 Bologna, ItalyDepartment of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena, ItalyDepartment of Pharmacy and Biotechnology, Alma Mater Studiorum—University of Bologna, Via Belmeloro 6, 40126 Bologna, ItalyDipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I, 43124 Parma, ItalyDipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I, 43124 Parma, ItalyDipartimento di Scienze degli Alimenti e del Farmaco, Università degli Studi di Parma, Parco Area delle Scienze 27/A, I, 43124 Parma, ItalyDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via G. Campi 287, 41125 Modena, ItalyDepartment of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena, ItalyDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via G. Campi 287, 41125 Modena, ItalyDepartment of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena, ItalyDepartment of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena, ItalyDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via G. Campi 287, 41125 Modena, ItalyDepartment of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 103, 41125 Modena, ItalyThe transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are the major downstream effectors in the Hippo pathway and are involved in cancer progression through modulation of the activity of TEAD (transcriptional enhanced associate domain) transcription factors. To exploit the advantages of drug repurposing in the search of new drugs, we developed a similar approach for the identification of new hits interfering with TEAD target gene expression. In our study, a 27-member in-house library was assembled, characterized, and screened for its cancer cell growth inhibition effect. In a secondary luciferase-based assay, only seven compounds confirmed their specific involvement in TEAD activity. <b>IA5</b> bearing a p-quinoid structure reduced the cytoplasmic level of phosphorylated YAP and the YAP–TEAD complex transcriptional activity and reduced cancer cell growth. <b>IA5</b> is a promising hit compound for TEAD activity modulator development.https://www.mdpi.com/1999-4923/14/2/391TEAD transcription factorleads repurposingluciferase assaychemoinformaticp-quinoid derivatives |
| spellingShingle | Angela Lauriola Elisa Uliassi Matteo Santucci Maria Laura Bolognesi Marco Mor Laura Scalvini Gian Marco Elisi Gaia Gozzi Lorenzo Tagliazucchi Gaetano Marverti Stefania Ferrari Lorena Losi Domenico D’Arca Maria Paola Costi Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing Library Pharmaceutics TEAD transcription factor leads repurposing luciferase assay chemoinformatic p-quinoid derivatives |
| title | Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing Library |
| title_full | Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing Library |
| title_fullStr | Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing Library |
| title_full_unstemmed | Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing Library |
| title_short | Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing Library |
| title_sort | identification of a quinone derivative as a yap tead activity modulator from a repurposing library |
| topic | TEAD transcription factor leads repurposing luciferase assay chemoinformatic p-quinoid derivatives |
| url | https://www.mdpi.com/1999-4923/14/2/391 |
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