9RMR

Crystal structure of RXR alpha LBD bound to a synthetic agonist FN558 and a coactivator fragment

これはPDB形式変換不可エントリーです。

9RMR の概要

• エントリーDOI: 10.2210/pdb9rmr/pdb
• 分子名称: Retinoic acid receptor RXR-alpha, Nuclear receptor coactivator 2, FN558, ... (4 entities in total)
• 機能のキーワード: inhibitor, nuclear receptor, rxra, drug, transcription factor, ligand binding domain, transcription
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28099.51

構造登録者

Morozov, V.,Nawa, F.,Merk, D. (登録日: 2025-06-18, 公開日: 2025-08-13, 最終更新日: 2025-08-27)

主引用文献

Nawa, F.,Kardanov, A.,Kasch, T.,Lewandowski, M.,Wein, T.,Hofner, G.,Marschner, J.A.,Morozov, V.,Merk, D.
Development of an RXR Agonist Scaffold with Pronounced Homodimer Preference.
J.Med.Chem., 68:16172-16187, 2025

PubMed Abstract: The activation of retinoid X receptors (RXRs) presents promising therapeutic potential in diverse conditions, such as cancer, inflammation, metabolic dysfunction, and neurodegeneration. However, RXRs play a central role in nuclear receptor signaling and act in various dimeric forms with multiple other ligand-activated transcription factors giving rise to promiscuous effects of RXR agonists. Here we identified a new RXR ligand chemotype addressing only part of RXR's molecular activities. Optimization provided a new RXR modulator scaffold fully activating the RXR homodimer with nanomolar potency but displaying markedly reduced RXR heterodimer activation compared to bexarotene. Co-crystal structure analysis revealed different molecular effects on the RXR LBD conformation than bexarotene possibly mediating the selective activity. The new RXR modulator type enables studies on selective RXR homodimer activation effects and suggests that different molecular mechanisms of RXR activity can be selectively addressed with ligands.

PubMed: 40704597
DOI: 10.1021/acs.jmedchem.5c01090

実験手法

X-RAY DIFFRACTION (1.65 Å)