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BioAssay: AID 593528

Agonist activity at human LRH-1 receptor assessed as TIF2 737-757 peptide recruitment by TR-FRET assay relative to control

The crystal structure of LRH-1 ligand binding domain bound to our previously reported agonist 3-(E-oct-4-en-4-yl)-1-phenylamino-2-phenyl-cis-bicyclo[3.3.0]oct-2-ene 5 is described. Two new classes of agonists in which the bridgehead anilino group from our first series was replaced with an alkoxy or 1-ethenyl group were designed, synthesized, and tested for activity in a peptide recruitment assay. more ..
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 Tested Compounds
 Tested Compounds
All(46)
 
 
Active(31)
 
 
Inactive(15)
 
 
 Tested Substances
 Tested Substances
All(46)
 
 
Active(31)
 
 
Inactive(15)
 
 
AID: 593528
Data Source: ChEMBL (743679)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-02-15
Modify Date: 2014-05-24

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Nuclear receptor subfamily 5 group A member 2; AltName: Full=Alpha-1-fetoprotein transcription factor; AltName: Full=B1-binding factor; Short=hB1F; AltName: Full=CYP7A promoter-binding factor; AltName: Full=Hepatocytic transcription factor; AltName: Full=Liver receptor homolog 1; Short=LRH-1
Description ..   
Protein Family: The ligand binding domain of the liver receptor homolog-1, a member of nuclear receptor superfamily,
Comment ..   

Gene:NR5A2     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 31
Description:
Title: Small molecule agonists of the orphan nuclear receptors steroidogenic factor-1 (SF-1, NR5A1) and liver receptor homologue-1 (LRH-1, NR5A2).

Abstract: The crystal structure of LRH-1 ligand binding domain bound to our previously reported agonist 3-(E-oct-4-en-4-yl)-1-phenylamino-2-phenyl-cis-bicyclo[3.3.0]oct-2-ene 5 is described. Two new classes of agonists in which the bridgehead anilino group from our first series was replaced with an alkoxy or 1-ethenyl group were designed, synthesized, and tested for activity in a peptide recruitment assay. Both new classes gave very active compounds, particularly against SF-1. Structure-activity studies led to excellent dual-LRH-1/SF-1 agonists (e.g., RJW100) as well as compounds selective for LRH-1 (RJW101) and SF-1 (RJW102 and RJW103). The series based on 1-ethenyl substitution was acid stable, overcoming a significant drawback of our original bridgehead anilino-substituted series. Initial studies on the regulation of gene expression in human cell lines showed excellent, reproducible activity at endogenous target genes.
(PMID: 21391689)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

Target Type: Target is a single protein chain

Result Definitions
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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 valueFloat
6EC50 standard valueEC50 standard valueFloatnM
7EC50 binding domainsEC50 binding domainsString
8pEC50 activity commentpEC50 activity commentString
9pEC50 standard flagpEC50 standard flagInteger
10pEC50 qualifierpEC50 qualifierString
11pEC50 published valuepEC50 published valueFloat
12pEC50 standard valuepEC50 standard valueFloat
13pEC50 binding domainspEC50 binding domainsString

* Activity Concentration.

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