6SJM

Crystal structure of the Retinoic Acid Receptor alpha in complex with compound 24 (JP175)

6SJM の概要

• エントリーDOI: 10.2210/pdb6sjm/pdb
• 分子名称: Retinoic acid receptor RXR-alpha, Nuclear receptor coactivator 2, 2-[4-[3,5-bis(trifluoromethyl)phenyl]phenyl]ethanoic acid, ... (4 entities in total)
• 機能のキーワード: rxra, steroid hormone receptor, inhibitor, structural genomics, structural genomics consortium, sgc, dna binding protein
• 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: 27909.27

構造登録者

Chaikuad, A.,Pollinger, J.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Merk, D.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2019-08-13, 公開日: 2019-09-18, 最終更新日: 2024-01-24)

主引用文献

Pollinger, J.,Schierle, S.,Gellrich, L.,Ohrndorf, J.,Kaiser, A.,Heitel, P.,Chaikuad, A.,Knapp, S.,Merk, D.
A Novel Biphenyl-based Chemotype of Retinoid X Receptor Ligands Enables Subtype and Heterodimer Preferences.
Acs Med.Chem.Lett., 10:1346-1352, 2019

PubMed Abstract: The nuclear retinoid X receptors (RXRs) are key ligand sensing transcription factors that serve as universal nuclear receptor heterodimer partners and are thus involved in numerous physiological processes. Therapeutic targeting of RXRs holds high potential but available RXR activators suffer from limited safety. Selectivity for RXR subtypes or for certain RXR heterodimers are promising strategies for safer RXR modulation. Here, we report systematic structure-activity relationship studies on biphenyl carboxylates as new RXR ligand chemotype. We discovered specific structural modifications that enhance potency on RXRs, govern subtype preference, and vary modulation of different RXR heterodimers. Fusion of these structural motifs enabled specific tuning of subtype preferential profiles with markedly improved potency. Our results provide further evidence that RXR subtype selective ligands can be designed and present a novel chemotype of RXR modulators that can be tuned for subtype and heterodimer preferences.

PubMed: 31531208
DOI: 10.1021/acsmedchemlett.9b00306

実験手法

X-RAY DIFFRACTION (2.52 Å)