9DON

Crystal structure of eIF4e in complex with Compound 5-PA

これはPDB形式変換不可エントリーです。

9DON の概要

• エントリーDOI: 10.2210/pdb9don/pdb
• 分子名称: Eukaryotic translation initiation factor 4E, 7N-METHYL-8-HYDROGUANOSINE-5'-DIPHOSPHATE, 2-[3-[[2-azanyl-7-[(5-chloranyl-1-benzofuran-2-yl)methyl]-6-oxidanylidene-1~{H}-purin-9-yl]methyl]phenyl]ethylphosphonic acid, ... (4 entities in total)
• 機能のキーワード: eif4e, translation initiation inhibitor, translation
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 45553.78

構造登録者

Meagher, J.L.,Stuckey, J.A. (登録日: 2024-09-19, 公開日: 2025-01-29)

主引用文献

Cardenas, E.L.,O'Rourke, R.L.,Menon, A.,Vega-Hernandez, G.,Meagher, J.,Stuckey, J.,Garner, A.L.
Second-Generation Cap Analogue Prodrugs for Targeting Aberrant Eukaryotic Translation Initiation Factor 4E Activity in Cancer.
Acs Med.Chem.Lett., 16:96-100, 2025

PubMed Abstract: Dysregulation of translation is a hallmark of cancer that enables rapid changes in cellular protein production to shape oncogenic phenotypes. Translation initiation is governed by the mGpppX cap-binding protein eukaryotic translation initiation factor 4E (eIF4E), the rate-limiting factor of cap-dependent translation initiation. eIF4E is overexpressed in many cancers and drives the production of oncoproteins that promote tumor growth and survival. Accordingly, eIF4E has been established as an attractive albeit challenging therapeutic target. Building upon our previous work of developing cell-permeable cap analogue prodrugs that inhibit eIF4E binding to the mGpppX cap, herein we disclose the design of second-generation cap analogues with alternative -9-substituted linkers which exhibit anticancer activity in BRAF mutant melanoma cell lines.

PubMed: 39811141
DOI: 10.1021/acsmedchemlett.4c00466

実験手法

X-RAY DIFFRACTION (2.091 Å)