8ZBH

Crystal structure of TEAD3 YAP binding domain with compound 3

これはPDB形式変換不可エントリーです。

8ZBH の概要

• エントリーDOI: 10.2210/pdb8zbh/pdb
• 関連するPDBエントリー: 8ZBG
• 分子名称: Transcriptional enhancer factor TEF-5, 1-[7-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1~{H}-isoquinolin-2-yl]propan-1-one (3 entities in total)
• 機能のキーワード: transcription factor, tead3, transcription
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 77187.64

構造登録者

Yoo, Y.,Kim, H. (登録日: 2024-04-26, 公開日: 2025-04-16)

主引用文献

Kim, J.,Kim, H.,Kim, J.,Cho, S.Y.,Moon, S.,Yoo, Y.,Kim, H.,Kim, J.K.,Jeon, H.,Namkung, W.,Han, G.,No, K.T.
Pan-Transcriptional Enhanced Associated Domain Palmitoylation Pocket Covalent Inhibitor.
J.Med.Chem., 67:18957-18968, 2024

PubMed Abstract: In the Hippo signaling pathway, the palmitoylated transcriptional enhanced associated domain (TEAD) protein interacts with the coactivator Yes-associated protein/PDZ-binding motif, leading to transcriptional upregulation of oncogenes such as Ctgf and Cyr61. Consequently, targeting the palmitoylation sites of TEAD has emerged as a promising strategy for treating TEAD-dependent cancers. Compound was identified using a structure-based drug design approach, leveraging the molecular insights gained from the known TEAD palmitoylation site inhibitor, K-975. Optimization of the initial hit compound resulted in the development of compound , a covalent pan-TEAD inhibitor characterized by high potency and oral bioavailability.

PubMed: 39487823
DOI: 10.1021/acs.jmedchem.4c01393

実験手法

X-RAY DIFFRACTION (2.6 Å)