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PDBsum entry 3ia6

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Transcription PDB id
3ia6
Jmol
Contents
Protein chain
254 a.a. *
Ligands
UNT ×2
Waters ×113
* Residue conservation analysis
PDB id:
3ia6
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
Resolution:
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
Date:
13-Jul-09     Release date:   13-Oct-09    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P37231  (PPARG_HUMAN) -  Peroxisome proliferator-activated receptor gamma
Seq:
Struc:
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.
 
  ABSTRACT  
 
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.