7A7H

Crystal structure of PPARgamma in complex with compound TK90

7A7H の概要

• エントリーDOI: 10.2210/pdb7a7h/pdb
• 分子名称: Peroxisome proliferator-activated receptor gamma, (2~{R})-2-[[4-[[4-methoxy-2-(trifluoromethyl)phenyl]methylcarbamoyl]phenyl]methyl]butanoic acid, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: complex, structural genomics, structural genomics consortium, sgc, dna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32139.26

構造登録者

Ni, X.,Kirchner, T.,Proschak, E.,Chaikuad, A.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2020-08-28, 公開日: 2021-08-04, 最終更新日: 2024-01-31)

主引用文献

Hartmann, M.,Bibli, S.I.,Tews, D.,Ni, X.,Kircher, T.,Kramer, J.S.,Kilu, W.,Heering, J.,Hernandez-Olmos, V.,Weizel, L.,Scriba, G.K.E.,Krait, S.,Knapp, S.,Chaikuad, A.,Merk, D.,Fleming, I.,Fischer-Posovszky, P.,Proschak, E.
Combined Cardioprotective and Adipocyte Browning Effects Promoted by the Eutomer of Dual sEH/PPAR gamma Modulator.
J.Med.Chem., 64:2815-2828, 2021

PubMed Abstract: The metabolic syndrome (MetS) is a constellation of cardiovascular and metabolic symptoms involving insulin resistance, steatohepatitis, obesity, hypertension, and heart disease, and patients suffering from MetS often require polypharmaceutical treatment. PPARγ agonists are highly effective oral antidiabetics with great potential in MetS, which promote adipocyte browning and insulin sensitization. However, the application of PPARγ agonists in clinics is restricted by potential cardiovascular adverse events. We have previously demonstrated that the racemic dual sEH/PPARγ modulator RB394 () simultaneously improves all risk factors of MetS in vivo. In this study, we identify and characterize the eutomer of . We provide structural rationale for molecular recognition of the eutomer. Furthermore, we could show that the dual sEH/PPARγ modulator is able to promote adipocyte browning and simultaneously exhibits cardioprotective activity which underlines its exciting potential in treatment of MetS.

PubMed: 33620196
DOI: 10.1021/acs.jmedchem.0c02063

実験手法

X-RAY DIFFRACTION (2.4 Å)