| Title: |
Toward the Discovery of a Novel Class of YAP–TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP–TEAD Protein–Protein Interface |
| Authors: |
Gibault, Floriane; Coevoet, Mathilde; Sturbaut, Manon; Farce, Amaury; Renault, Nicolas; Allemand, Frédéric; Guichou, Jean-François; Drucbert, Anne Sophie; Foulon, Catherine; Magnez, Romain; Thuru, Xavier; Corvaisier, Mathieu; Huet, Guillemette; Chavatte, Philippe; Melnyk, Patricia; Bailly, Fabrice; Cotelle, Philippe |
| Contributors: |
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc); Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille; Lille Inflammation Research International Center - U 995 (LIRIC); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Centre de Biochimie Structurale Montpellier (CBS); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS); Université de Lille; ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010) |
| Source: |
ISSN: 2072-6694. |
| Publisher Information: |
CCSD; MDPI |
| Publication Year: |
2018 |
| Collection: |
Université de Montpellier: HAL |
| Subject Terms: |
binding assays; molecular docking; protein-protein interaction; anticancer; YAP-TEAD disruption; [CHIM.THER]Chemical Sciences/Medicinal Chemistry; [CHIM.CHEM]Chemical Sciences/Cheminformatics; [SDV.CAN]Life Sciences [q-bio]/Cancer |
| Description: |
International audience ; 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 hYAP 50-71-hTEAD1 209-426 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 assay was discovered. This hit also decreased mRNA levels of TEAD target genes. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/29738494; PUBMED: 29738494 |
| DOI: |
10.3390/cancers10050140 |
| Availability: |
https://hal.science/hal-02060686; https://hal.science/hal-02060686v1/document; https://hal.science/hal-02060686v1/file/cancers-10-00140.pdf; https://doi.org/10.3390/cancers10050140 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.E675E0F6 |
| Database: |
BASE |