Bookmark and Share
BioAssay: AID 728043

Agonist activity at PPARalpha (unknown origin)

Identification of a series of imidazo[4,5-c]pyridin-4-one derivatives that act as dual angiotensin II type 1 (AT1) receptor antagonists and peroxisome proliferator-activated receptor-gamma (PPARgamma) partial agonists is described. Starting from a known AT1 antagonist template, conformational restriction was introduced by incorporation of an indane ring that when combined with appropriate more ..
_
   
 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 728043
Data Source: ChEMBL (940609)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-11-07
Modify Date: 2014-08-27

Data Table ( Complete ):           View All Data
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: Design, synthesis, and evaluation of imidazo[4,5-c]pyridin-4-one derivatives with dual activity at angiotensin II type 1 receptor and peroxisome proliferator-activated receptor-gamma.

Abstract: Identification of a series of imidazo[4,5-c]pyridin-4-one derivatives that act as dual angiotensin II type 1 (AT1) receptor antagonists and peroxisome proliferator-activated receptor-gamma (PPARgamma) partial agonists is described. Starting from a known AT1 antagonist template, conformational restriction was introduced by incorporation of an indane ring that when combined with appropriate substitution at the imidazo[4,5-c]pyridin-4-one provided novel series 5 possessing the desired dual activity. The mode of interaction of this series with PPARgamma was corroborated through the X-ray crystal structure of 12b bound to the human PPARgamma ligand binding domain. Modulation of activity at both receptors through substitution at the pyridone nitrogen led to the identification of potent dual AT1 antagonists/PPARgamma partial agonists. Among them, 21b was identified possessing potent dual pharmacology (AT1 IC(50) = 7 nM; PPARgamma EC(50) = 295 nM, 27% max) and good ADME properties.
(PMID: 23265881)
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1EC50*EC50 PubChem standard valueFloatμM
2EC50 activity commentEC50 activity commentString
3EC50 standard flagEC50 standard flagInteger
4EC50 qualifierEC50 qualifierString
5EC50 published valueEC50 published valueFloatnM
6EC50 standard valueEC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View All Data
Classification
PageFrom: