Title :

Toward the Discovery of a Novel Class of YAP⁻TEAD Interaction Inhibitors by Virtual Screening Approach Targeting YAP⁻TEAD Protein⁻Protein Interface.

Author(s) :

Gibault, Floriane [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Coevoet, Mathilde [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Sturbaut, Manon [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Renault, Nicolas [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Lille Inflammation Research International Center - U 995 [LIRIC]
Allemand, Frederic [Auteur]
Centre de Biochimie Structurale [Montpellier] [CBS]
Guichou, Jean-Francois [Auteur]
Centre de Biochimie Structurale [Montpellier] [CBS]
Drucbert, Anne-Sophie [Auteur]
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Foulon, Catherine [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Magnez, Romain [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Thuru, Xavier [Auteur]
Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer
Corvaisier, Matthieu [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Huet, Guillemette [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Chavatte, Philippe [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Melnyk, Patricia [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Bailly, Fabrice [Auteur]
Unité de Catalyse et de Chimie du Solide (UCCS) - UMR 8181
Unité de Catalyse et Chimie du Solide - UMR 8181 [UCCS]
Cotelle, Philippe [Auteur]

Journal title :

Cancers

Abbreviated title :

Cancers (Basel)

Volume number :

10

Publication date :

2018-05

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

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 ...
Show more >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 assay was discovered. This hit also decreased mRNA levels of TEAD target genes.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille
Inserm

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Research team(s) :

Modélisation biopharmaceutique et pharmacocinétique

Submission date :

2019-02-27T13:39:02Z
2021-06-07T07:32:19Z
2021-06-07T09:04:59Z