8ZNN
X-ray structure of human PPAR delta ligand binding domain in complex with a synthetic agonist 16a
This is a non-PDB format compatible entry.
Summary for 8ZNN
| Entry DOI | 10.2210/pdb8znn/pdb |
| Descriptor | Peroxisome proliferator-activated receptor delta, 6-[2-[[2-[4-(trifluoromethyloxy)phenyl]benzimidazol-1-yl]methyl]phenoxy]hexanoic acid (3 entities in total) |
| Functional Keywords | agonist, ppar, nuclear protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 31387.43 |
| Authors | |
| Primary citation | Feng, Z.,Xie, J.,Hou, D.,Fu, Z.,Sun, S.,Liu, X.,Sun, G.,Zheng, R.,Liu, L.,Xu, Q.,Wen, X.,Zhang, D.,Yuan, H.,Sun, H.,Dai, L. Design, Synthesis, and Biological Evaluation of Arylimidazole Derivatives as Potent PPAR delta Agonists for the Treatment of Renal Fibrosis. J.Med.Chem., 69:4469-4492, 2026 Cited by PubMed Abstract: Peroxisome proliferator-activator receptor δ (PPARδ) is ubiquitously expressed in the kidney, and its agonists are increasingly being recognized as a potential therapeutic strategy for renal diseases. In this work, we developed a series of arylimidazole derivatives as potent PPARδ agonists. Among them, compound exhibited potent PPARδ agonistic activity (EC = 0.50 nM) and high selectivity over PPARα/γ and some other nuclear receptors. The X-ray cocrystal structure revealed the binding mode of and PPARδ at 1.94 Å resolution. Remarkably, compound exhibited acceptable pharmacokinetic properties and good safety profiles in vivo and showed antirenal fibrosis effects in a dose-dependent manner in a mouse model of unilateral ureteral obstruction. Mechanistically, activated PPARδ to restore fatty acid oxidation to attenuate TGF-β1-induced renal fibroblast activation. Collectively, warrants further investigation as a promising drug candidate for treating renal fibrosis. PubMed: 41667192DOI: 10.1021/acs.jmedchem.5c03132 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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