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BioAssay: AID 722378

Transactivation of GAL4-fused human PPARalpha ligand binding domain expressed in HepG2 cells up to 10 uM after 20 hrs by luciferase reporter gene assay

The preparation of a series of 2-(aryloxy)-3-phenylpropanoic acids, resulting from the introduction of different substituents into the biphenyl system of the previously reported peroxisome proliferator-activated receptor alpha/gamma (PPARalpha/gamma) dual agonist 1, allowed the identification of new ligands with higher potency on PPARalpha and fine-tuned moderate PPARgamma activity. For the most more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Inactive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 722378
Data Source: ChEMBL (934944)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-11-07
Modify Date: 2014-05-26

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Peroxisome proliferator-activated receptor alpha; Short=PPAR-alpha; AltName: Full=Nuclear receptor subfamily 1 group C member 1
Description ..   
Protein Family: The ligand binding domain of peroxisome proliferator-activated receptors
Comment ..   

Gene:PPARA     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: New 2-(aryloxy)-3-phenylpropanoic acids as peroxisome proliferator-activated receptor alpha/gamma dual agonists able to upregulate mitochondrial carnitine shuttle system gene expression.

Abstract: The preparation of a series of 2-(aryloxy)-3-phenylpropanoic acids, resulting from the introduction of different substituents into the biphenyl system of the previously reported peroxisome proliferator-activated receptor alpha/gamma (PPARalpha/gamma) dual agonist 1, allowed the identification of new ligands with higher potency on PPARalpha and fine-tuned moderate PPARgamma activity. For the most promising stereoisomer (S)-16, X-ray and calorimetric studies in PPARgamma revealed, at high ligand concentration, the presence of two molecules simultaneously bound to the receptor. On the basis of these results and docking experiments in both receptor subtypes, a molecular explanation was provided for its different behavior as a full and partial agonist of PPARalpha and PPARgamma, respectively. The effects of (S)-16 on mitochondrial acylcarnitine carrier and carnitine-palmitoyl-transferase 1 gene expression, two key components of the carnitine shuttle system, were also investigated, allowing the hypothesis of a more beneficial pharmacological profile of this compound compared to the less potent PPARalpha agonist fibrates currently used in therapy.
(PMID: 23171045)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

Assay Test Type: In vitro

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat
5Activity standard valueActivity standard valueFloat

Data Table (Concise)
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