| Added by | alainmange |
|---|---|
| Group name | PlateformePP2I |
| Item Type | Journal Article |
| Title | Design, Synthesis and Evaluation of a Series of 1,5-Diaryl-1,2,3-triazole-4-carbohydrazones as Inhibitors of the YAP-TAZ/TEAD Complex |
| Creator | Bailly et al. |
| Author | Fabrice Bailly |
| Author | Floriane Gibault |
| Author | Manon Sturbaut |
| Author | Mathilde Coevoet |
| Author | Martine Pugnière |
| Author | Ashley Burtscher |
| Author | Patricia Melnyk |
| Author | Wanjin Hong |
| Author | Brian P. Rubin |
| Author | Ajaybabu V. Pobbati |
| Author | Jean-François Guichou |
| Author | Philippe Cotelle |
| Abstract | Starting from our previously reported hit, a series of 1,5-diaryl-1,2,3-triazole-4-carbohydrazones was synthesized and evaluated as inhibitors of the YAP/TAZ-TEAD complex. Binding to hTEAD2 of our compounds was evidenced by nanodifferential scanning fluorimetry and they were also shown by polarization fluorescence to disrupt to some extent YAP-TEAD interaction. They displayed micromolar inhibition in a luciferase gene reporter assay in transfected HEK293T cells and decreased mRNAs levels of TEAD target genes measured by RTqPCR in MDA-MB231 cells. In spite of limiting cytotoxicities, careful analysis of the biological data let emerge some new hits as the starting points for future design aimed at improving YAP-TEAD disruption. |
| Publication | ChemMedChem |
| Date | 2021-05-25 |
| Journal Abbr | ChemMedChem |
| Language | eng |
| DOI | 10.1002/cmdc.202100153 |
| ISSN | 1860-7187 |
| Library Catalog | PubMed |
| Extra | PMID: 34032019 |
| Tags | antitumor agents, Hippo pathway, protein-protein interactions, TEAD binding, YAP-TEAD inhibition, author, original, pp2i |
| Date Added | 2021/06/03 - 16:33:17 |
| Date Modified | 2021/06/03 - 16:37:15 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
