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

ChemMedChem. 2021 May 25. doi: 10.1002/cmdc.202100153. Online ahead of print.ABSTRACTStarting 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.PMID:34032019 | DOI:10.1002/cmdc.202100153

Source: ChemMedChem - May 25, 2021 Category: Chemistry Authors: Fabrice Bailly Floriane Gibault Manon Sturbaut Mathilde Coevoet Martine Pugni ère Ashley Burtscher Fr édéric Allemand Patricia Melnyk Wanjin Hong Brian P Rubin Ajaybabu V Pobbati Jean-Fran çois Guichou Philippe Cotelle Source Type: research