2J14

3,4,5-Trisubstituted Isoxazoles as Novel PPARdelta Agonists: Part2

2J14 の概要

• エントリーDOI: 10.2210/pdb2j14/pdb
• 関連するPDBエントリー: 1GWX 1Y0S 2AWH 2B50 2BAW 2GWX 3GWX
• 分子名称: PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR DELTA, (3-{4-[2-(2,4-DICHLORO-PHENOXY)-ETHYLCARBAMOYL]-5-PHENYL-ISOXAZOL-3-YL}-PHENYL)-ACETIC ACID (3 entities in total)
• 機能のキーワード: transcription, nuclear receptor fold, transcription regulation, ppar, zinc, receptor, activator, fatty acids, nuclear protein, alternative splicing, zinc-finger, dna-binding, metal-binding
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Nucleus: Q03181
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66384.38

構造登録者

Epple, R.,Azimioara, M.,Russo, R.,Xie, Y.,Wang, X.,Cow, C.,Wityak, J.,Karanewsky, D.,Bursulaya, B.,Kreusch, A.,Tuntland, T.,Gerken, A.,Iskandar, M.,Saez, E.,Seidel, H.M.,Tian, S.S. (登録日: 2006-08-08, 公開日: 2006-09-06, 最終更新日: 2023-12-13)

主引用文献

Epple, R.,Azimioara, M.,Russo, R.,Xie, Y.,Wang, X.,Cow, C.,Wityak, J.,Karanewsky, D.,Bursulaya, B.,Kreusch, A.,Tuntland, T.,Gerken, A.,Iskandar, M.,Saez, E.,Seidel, H.M.,Tian, S.S.
3,4,5-Trisubstituted Isoxazoles as Novel Ppardelta Agonists. Part 2
Bioorg.Med.Chem.Lett., 16:5488-, 2006

PubMed Abstract: A series of PPARdelta-selective agonists was investigated and optimized for a favorable in vivo pharmacokinetic profile. Isoxazole LCI765 (17d) was found to be a potent and selective PPARdelta agonist with good in vivo PK properties in mouse (C(max)=5.1 microM, t(1/2)=3.1 h). LCI765 regulated expression of genes involved in energy homeostasis in relevant tissues when dosed orally in C57BL6 mice. A co-crystal structure of compound LCI765 and the LBD of PPARdelta is discussed.

PubMed: 16931011
DOI: 10.1016/J.BMCL.2006.08.052

実験手法

X-RAY DIFFRACTION (2.8 Å)