9M1C

Vitamin D receptor complex with a triphenylpropylsilane derivative

これはPDB形式変換不可エントリーです。

9M1C の概要

• エントリーDOI: 10.2210/pdb9m1c/pdb
• 分子名称: Vitamin D3 receptor, Mediator of RNA polymerase II transcription subunit 1, (4~{S})-5-[4-[[4-(2-ethyl-2-oxidanyl-butoxy)-3-methyl-phenyl]-methyl-phenyl-silyl]-2-methyl-phenoxy]-4-oxidanyl-pentanoic 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: 32716.69

構造登録者

Thilakarathne, N.M.H.N.,Hanazono, Y.,Ito, N.,Kagechika, H.,Fujii, S. (登録日: 2025-02-25, 公開日: 2025-06-11, 最終更新日: 2025-06-25)

主引用文献

Mudiyanselage, H.N.T.N.,Misawa, T.,Ochiai, K.,Demizu, Y.,Hanazono, Y.,Ito, N.,Fujii, S.
Structure-activity relationship and crystallographic analyses of non-secosteroidal vitamin D receptor ligands bearing diphenylsilane core as a hydrophobic pharmacophore.
Bioorg.Med.Chem., 128:118261-118261, 2025

PubMed Abstract: Vitamin D receptor (VDR) is an attractive target of drug discovery for multiple diseases. In this study, we systematically designed and synthesized a series of diphenylsilane derivatives with diverse hydrophobic substituents and investigated their structure-activity relationship (SAR) as VDR agonists. The SAR study revealed that the activity is dependent on the type of substituent and the position of substitution, and the diethyl-di-m-tolylsilane scaffold was identified as the most suitable hydrophobic core structure of this type of VDR ligands. Interestingly, the small structural difference between n-propyl and allyl substituents resulted in a large difference in the activity. Comparison of the co-crystal structures of 14 diphenylsilane compounds, including less potent compounds, bound to the rat VDR ligand-binding domain suggested that the differences in activity are due to a combination of factors, including differences in hydrophilic and hydrophobic interactions, and ligand conformations.

PubMed: 40494220
DOI: 10.1016/j.bmc.2025.118261

実験手法

X-RAY DIFFRACTION (1.67 Å)