9VOL

Vitamin D receptor complex with a 4-{4-(m-carboran-1-yl)-2-methylphenoxy}butanoic acid derivative

これはPDB形式変換不可エントリーです。

9VOL の概要

• エントリーDOI: 10.2210/pdb9vol/pdb
• 分子名称: Vitamin D3 receptor, Mediator of RNA polymerase II transcription subunit 1, 4-[4-{7-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-1,7-dicarba-closo-dodecaboran-1-yl}-2-methylphenoxy]butyric acid, ... (4 entities in total)
• 機能のキーワード: vitamin d receptor, transcription
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32744.49

構造登録者

Mudiyanselage, H.N.T.N.,Hanazono, Y.,Ito, N.,Kagechika, H.,Fujii, S. (登録日: 2025-07-01, 公開日: 2025-12-03)

主引用文献

Mudiyanselage, H.N.T.N.,Misawa, T.,Ochiai, K.,Demizu, Y.,Hanazono, Y.,Ito, N.,Fujii, S.
Design, synthesis and structural development of nonsecosteroidal VDR ligands based on the C,C'-diphenyl-m-carborane scaffold.
Eur.J.Med.Chem., 302:118320-118320, 2025

PubMed Abstract: Nonsecosteroidal vitamin D receptor (VDR) ligands are promising drug candidates for multiple diseases, including osteoporosis, psoriasis, and certain cancers. We report here the design, synthesis, biological evaluation and crystallographic analysis of a series of 1,7-diphenyl-m-carborane derivatives as novel nonsecosteroidal VDR ligands. We found that the 1,7-diphenyl-m-carborane framework is a promising hydrophobic core of VDR ligands, and developed a series of potent compounds such as 12b and 13a. Interestingly, compounds with different chain length exhibited similar potencies. X-Ray co-crystal structure analysis revealed that the developed compounds exhibited various different interaction patterns depending on the structure of the carboxyalkyl chain, indicating that the ligand-binding pocket of the VDR possesses sufficient conformational plasticity to accommodate a wide variety of ligands without compromising activity. The developed carborane derivatives are promising leads for further structural development, and the findings on the diversity of binding modes will be helpful in the design of other VDR ligands.

PubMed: 41205515
DOI: 10.1016/j.ejmech.2025.118320

実験手法

X-RAY DIFFRACTION (1.75 Å)