8A0V

Crystal structure of TEAD3 in complex with CPD2

8A0V の概要

• エントリーDOI: 10.2210/pdb8a0v/pdb
• 分子名称: Transcriptional enhancer factor TEF-5, MYRISTIC ACID, DIMETHYL SULFOXIDE, ... (6 entities in total)
• 機能のキーワード: inhibitor, complex, transcription
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 104611.46

構造登録者

Scheufler, C.,Kallen, J. (登録日: 2022-05-30, 公開日: 2022-08-17, 最終更新日: 2024-10-16)

主引用文献

Furet, P.,Bordas, V.,Le Douget, M.,Salem, B.,Mesrouze, Y.,Imbach-Weese, P.,Sellner, H.,Voegtle, M.,Soldermann, N.,Chapeau, E.,Wartmann, M.,Scheufler, C.,Fernandez, C.,Kallen, J.,Guagnano, V.,Chene, P.,Schmelzle, T.
The First Class of Small Molecules Potently Disrupting the YAP-TEAD Interaction by Direct Competition.
Chemmedchem, 17:e202200303-e202200303, 2022

PubMed Abstract: Inhibition of the YAP-TEAD protein-protein interaction is an attractive therapeutic concept under intense investigation with the objective to treat cancers associated with a dysregulation of the Hippo pathway. However, owing to the very extended surface of interaction of the two proteins, the identification of small drug-like molecules able to efficiently prevent YAP from binding to TEAD by direct competition has been elusive so far. We disclose here the discovery of the first class of small molecules potently inhibiting the YAP-TEAD interaction by binding at one of the main interaction sites of YAP at the surface of TEAD. These inhibitors, providing a path forward to pharmacological intervention in the Hippo pathway, evolved from a weakly active virtual screening hit advanced to high potency by structure-based design.

PubMed: 35950546
DOI: 10.1002/cmdc.202200303

実験手法

X-RAY DIFFRACTION (2.699 Å)