PDBsum entry 3ia6

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Transcription PDB id
Protein chain
254 a.a. *
UNT ×2
Waters ×113
* Residue conservation analysis
PDB id:
Name: Transcription
Title: X-ray crystal structure of the nuclear hormone receptor ppar-gamma in a complex with a ppar gamma/alpha dual agonist
Structure: Peroxisome proliferator-activated receptor gamma. Chain: a, b. Fragment: unp residue 235-505. Synonym: ppar-gamma, nuclear receptor subfamily 1 group c member 3. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pparg, nr1c3. Expressed in: escherichia coli. Expression_system_taxid: 562
2.31Å     R-factor:   0.241     R-free:   0.297
Authors: J.F.Ohren
Key ref: A.Casimiro-Garcia et al. (2009). Synthesis and evaluation of novel alpha-heteroaryl-phenylpropanoic acid derivatives as PPARalpha/gamma dual agonists. Bioorg Med Chem, 17, 7113-7125. PubMed id: 19783444
13-Jul-09     Release date:   13-Oct-09    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P37231  (PPARG_HUMAN) -  Peroxisome proliferator-activated receptor gamma
505 a.a.
254 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     4 terms  


Bioorg Med Chem 17:7113-7125 (2009)
PubMed id: 19783444  
Synthesis and evaluation of novel alpha-heteroaryl-phenylpropanoic acid derivatives as PPARalpha/gamma dual agonists.
A.Casimiro-Garcia, C.F.Bigge, J.A.Davis, T.Padalino, J.Pulaski, J.F.Ohren, P.McConnell, C.D.Kane, L.J.Royer, K.A.Stevens, B.Auerbach, W.Collard, C.McGregor, K.Song.
The synthesis of a new series of phenylpropanoic acid derivatives incorporating an heteroaryl group at the alpha-position and their evaluation for binding and activation of PPARalpha and PPARgamma are presented in this report. Among the new compounds, (S)-3-{4-[3-(5-methyl-2-phenyl-oxazol-4-yl)-propyl]-phenyl}-2-1,2,3-triazol-2-yl-propionic acid (17j), was identified as a potent human PPARalpha/gamma dual agonist (EC(50)=0.013 and 0.061 microM, respectively) with demonstrated oral bioavailability in rat and dog. 17j was shown to decrease insulin levels, plasma glucose, and triglycerides in the ZDF female rat model. In the human apolipoprotein A-1/CETP transgenic mouse model 17j produced increases in hApoA1 and HDL-C and decreases in plasma triglycerides. The increased potency for binding and activation of both PPAR subtypes observed with 17j when compared to previous analogs in this series was explained based on results derived from crystallographic and modeling studies.