5ZXI

Co-crystal structure of an Inhibitor in complex with human PPARdelta LBD

5ZXI の概要

• エントリーDOI: 10.2210/pdb5zxi/pdb
• 関連するPDBエントリー: 5XMX
• 分子名称: Peroxisome proliferator-activated receptor delta, 6-[2-({2-[4-(furan-2-yl)phenyl]-5-methyl-1H-imidazol-1-yl}methyl)phenoxy]hexanoic acid (3 entities in total)
• 機能のキーワード: ppardelta, inhibitor compound co-crystal structure, transcription
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63750.11

構造登録者

Rani, S.T.,Laxminarasimhan, A.,Senaiar, R.S.,Krishnamurthy, N. (登録日: 2018-05-21, 公開日: 2019-04-03, 最終更新日: 2024-03-27)

主引用文献

Lagu, B.,Kluge, A.F.,Tozzo, E.,Fredenburg, R.,Bell, E.L.,Goddeeris, M.M.,Dwyer, P.,Basinski, A.,Senaiar, R.S.,Jaleel, M.,Tiwari, N.K.,Panigrahi, S.K.,Krishnamurthy, N.R.,Takahashi, T.,Patane, M.A.
Selective PPAR delta Modulators Improve Mitochondrial Function: Potential Treatment for Duchenne Muscular Dystrophy (DMD).
ACS Med Chem Lett, 9:935-940, 2018

PubMed Abstract: The X-ray structure of the previously reported PPARδ modulator bound to the ligand binding domain (LBD) revealed that the amide moiety in exists in the thermodynamically disfavored -amide orientation. Isosteric replacement of the -amide with five-membered heterocycles led to the identification of imidazole (MA-0204), a potent, selective PPARδ modulator with good pharmacokinetic properties. MA-0204 was tested in mice and in patient-derived muscle myoblasts (from Duchenne Muscular Dystrophy (DMD) patients); altered the expression of PPARδ target genes and improved fatty acid oxidation, which supports the therapeutic hypothesis for the study of MA-0204 in DMD patients.

PubMed: 30258544
DOI: 10.1021/acsmedchemlett.8b00287

実験手法

X-RAY DIFFRACTION (2.1 Å)