1KNU

LIGAND BINDING DOMAIN OF THE HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA IN COMPLEX WITH A SYNTHETIC AGONIST

1KNU の概要

• エントリーDOI: 10.2210/pdb1knu/pdb
• 関連するPDBエントリー: 1PRG 2PRG
• 分子名称: PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA, (S)-3-(4-(2-CARBAZOL-9-YL-ETHOXY)-PHENYL)-2-ETHOXY-PROPIONIC ACID (3 entities in total)
• 機能のキーワード: ppar, nuclear receptor, transcription, gene regulation, agonist complex, dna binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: P37231
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63046.26

構造登録者

Svensson, L.A.,Mortensen, S.B.,Fleckner, J.,Woeldike, H.F. (登録日: 2001-12-19, 公開日: 2002-12-19, 最終更新日: 2023-10-25)

主引用文献

Sauerberg, P.,Pettersson, I.,Jeppesen, L.,Bury, P.S.,Mogensen, J.P.,Wassermann, K.,Brand, C.L.,Sturis, J.,Woldike, H.F.,Fleckner, J.,Andersen, A.-S.T.,Mortensen, S.B.,Svensson, L.A.,Rasmussen, H.B.,Lehmann, S.V.,Polivka, Z.,Sindelar, K.,Panajotova, V.,Ynddal, L.,Wulff, E.M.
Novel tricyclic-alpha-alkyloxyphenylpropionic acids: dual PPARalpha/gamma agonists with hypolipidemic and antidiabetic activity
J.MED.CHEM., 45:789-804, 2002

PubMed Abstract: Synthesis and structure-activity relationships of tricyclic alpha-ethoxy-phenylpropionic acid derivatives guided by in vitro PPARalpha and PPARgamma transactivation data and computer modeling led to the identification of the novel carbazole analogue, 3q, with dual PPARalpha (EC(50) = 0.36 microM) and PPARgamma (EC(50) = 0.17 microM) activity in vitro. Ten days treatment of db/db mice with 3q improved the insulin sensitivity, as measured by OGTT, better than that seen with both pioglitazone and rosiglitazone treatment, suggesting in vivo PPARgamma activity. Likewise, 3q lowered plasma triglycerides and cholesterol in high cholesterol fed rats after 4 days treatment, indicating in vivo PPARalpha activity. Investigations of the pharmacokinetics of selected compounds suggested that extended drug exposure improved the in vivo activity of in vitro active compounds.

PubMed: 11831892
DOI: 10.1021/jm010964g

実験手法

X-RAY DIFFRACTION (2.5 Å)