Cancers, Vol. 10, Pages 140: Toward the Discovery of a Novel Class of YAP –TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP–TEAD Protein–Protein Interface
Cancers, Vol. 10, Pages 140: Toward the Discovery of a Novel Class of YAP–TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP–TEAD Protein–Protein Interface
Cancers doi: 10.3390/cancers10050140
Authors:
Floriane Gibault
Mathilde Coevoet
Manon Sturbaut
Amaury Farce
Nicolas Renault
Frédéric Allemand
Jean-François Guichou
Anne-Sophie Drucbert
Catherine Foulon
Romain Magnez
Xavier Thuru
Matthieu Corvaisier
Guillemette Huet
Philippe Chavatte
Patricia Melnyk
Fabrice Bailly
Philippe Cotelle
Intrinsically disordered protein YAP (yes-associated protein) interacts with TEADs transcriptional factors family (transcriptional enhancer associated domain) creating three interfaces. Interface 3, between the Ω-loop of YAP and a shallow pocket of TEAD was identified as the most important TEAD zone for YAP-TEAD interaction. Using the first X-ray structure of the hYAP50–71-hTEAD1209–426 complex (PDB 3KYS) published in 2010, a protein-protein interaction inhibitors-enriched library (175,000 chemical compounds) was screened against this hydrophobic pocket of TEAD. Four different chemical families have been identified and evaluated using biophysical techniques (thermal shift assay, microscale thermophoresis) and in cellulo assays (luciferase activity in transfected HEK293 cells, RTqPCR in MDA-MB231 cells). A first promising hit with micromolar inhibition in the luciferase gene reporter assa...
Source: Cancers - Category: Cancer & Oncology Authors: Floriane Gibault Mathilde Coevoet Manon Sturbaut Amaury Farce Nicolas Renault Fr édéric Allemand Jean-Fran çois Guichou Anne-Sophie Drucbert Catherine Foulon Romain Magnez Xavier Thuru Matthieu Corvaisier Guillemette Huet Philippe Chavatte Patricia Mel Tags: Article Source Type: research