3OOK

Crystal structure of human FXR in complex with 4-({(2S)-2-[2-(4-chlorophenyl)-5,6-difluoro-1H-benzimidazol-1-yl]-2-cyclohexylacetyl}amino)-3,5-difluorobenzoic acid

3OOK の概要

• エントリーDOI: 10.2210/pdb3ook/pdb
• 関連するPDBエントリー: 3OKH 3OKI 3OLF 3OMK 3OMM 3OOF
• 分子名称: Bile acid receptor, peptide of Nuclear receptor coactivator 1, 4-({(2S)-2-[2-(4-chlorophenyl)-5,6-difluoro-1H-benzimidazol-1-yl]-2-cyclohexylacetyl}amino)-3,5-difluorobenzoic acid, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, cholesterol, bile acid, dna-binding, nucleus, receptor, transcription, ligand binding domain transcription regulation, coactivator, fxr alternative splicing, hormone receptor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus (Probable): Q96RI1; Nucleus (By similarity): Q15788
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 58900.31

構造登録者

Rudolph, M.G. (登録日: 2010-08-31, 公開日: 2011-01-19, 最終更新日: 2024-04-03)

主引用文献

Richter, H.G.F.,Benson, G.M.,Bleicher, K.H.,Blum, D.,Chaput, E.,Clemann, N.,Feng, S.,Gardes, C.,Grether, U.,Hartman, P.,Kuhn, B.,Martin, R.E.,Plancher, J.M.,Rudolph, M.G.,Schuler, F.,Taylor, S.
Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties
Bioorg.Med.Chem.Lett., 21:1134-1140, 2011

PubMed Abstract: Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-{(S)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after oral administration to LDL receptor deficient mice.

PubMed: 21269824
DOI: 10.1016/j.bmcl.2010.12.123

実験手法

X-RAY DIFFRACTION (2.29 Å)