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BioAssay: AID 593537

Agonist activity at mouse SF-1 expressed in HEK293 cells assessed as increase in SHP mRNA levels at 10 uM after 24 hrs by RT-qPCR method

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(4)
 
 
Active(2)
 
 
Inactive(2)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Active(2)
 
 
Inactive(2)
 
 
AID: 593537
Data Source: ChEMBL (743688)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-02-15
Modify Date: 2014-05-24

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Steroidogenic factor 1; Short=SF-1; Short=STF-1; AltName: Full=Adrenal 4-binding protein; AltName: Full=Embryonal LTR-binding protein; Short=ELP; AltName: Full=Embryonal long terminal repeat-binding protein; AltName: Full=Fushi tarazu factor homolog 1; AltName: Full=Nuclear receptor subfamily 5 group A member 1; AltName: Full=Steroid hormone receptor Ad4BP; AltName: Full=Steroid hydroxylase positive regulator
Description ..   
Protein Family: The ligand binding domain of nuclear receptor steroidogenic factor 1, a member of nuclear receptor superfamily
Comment ..   

Gene:NR5A1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 2
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)
Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Assay Cell Type: HEK293

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)
Classification
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