3FXV

Identification of an N-oxide pyridine GW4064 analogue as a potent FXR agonist

3FXV の概要

• エントリーDOI: 10.2210/pdb3fxv/pdb
• 分子名称: NR1H4 protein, 12-meric peptide from Nuclear receptor coactivator 1, 6-(4-{[3-(3,5-dichloropyridin-4-yl)-5-(1-methylethyl)isoxazol-4-yl]methoxy}-2-methylphenyl)-1-methyl-1H-indole-3-carbox ylic acid, ... (4 entities in total)
• 機能のキーワード: nuclear receptor, cholesterol, bile acid, dna-binding, metal-binding, nucleus, receptor, transcription, transcription regulation, zinc, zinc-finger, activator, acyltransferase, alternative splicing, chromosomal rearrangement, phosphoprotein, polymorphism, proto-oncogene, transferase, ubl conjugation, hormone receptor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : Q15788
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29311.53

構造登録者

Feng, S.,Yang, M.,He, Y.,Chen, L.,Zhang, Z.,Wang, Z.,Hong, D.,Richter, H.,Benson, G.M.,Bleicher, K.,Grether, U.,Martin, R.,Plancher, J.-M.,Kuhn, B.,Rudolph, M.G. (登録日: 2009-01-21, 公開日: 2009-04-14, 最終更新日: 2024-04-03)

主引用文献

Feng, S.,Yang, M.,Zhang, Z.,Wang, Z.,Hong, D.,Richter, H.,Benson, G.M.,Bleicher, K.,Grether, U.,Martin, R.E.,Plancher, J.-M.,Kuhn, B.,Rudolph, M.G.,Chen, L.
Identification of an N-oxide pyridine GW4064 analog as a potent FXR agonist
Bioorg.Med.Chem.Lett., 19:2595-2598, 2009

PubMed Abstract: According to the docking studies and the analysis of a co-crystal structure of GW4064 with FXR, a series of 3-aryl heterocyclic isoxazole analogs were designed and synthesized. N-Oxide pyridine analog (7b) was identified as a promising FXR agonist with potent binding affinity and good efficacy, supporting our hypothesis that through an additional hydrogen bond interaction between the pyridine substituent of isoxazole analogs and Tyr373 and Ser336 of FXR, binding affinity and functional activity could be improved.

PubMed: 19328688
DOI: 10.1016/j.bmcl.2009.03.008

実験手法

X-RAY DIFFRACTION (2.26 Å)