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BioAssay: AID 703192

Transactivational agonist activity at human LXRbeta transfected in HEK293 cells expressing CMX-Gal4N assessed as luciferase activity at 30 uM after 16 hrs by reporter gene assay

To obtain novel transrepression-selective liver X receptor (LXR) ligands, we adopted a strategy of reducing the transactivational agonistic activity of the 5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one derivative 10, which exhibits LXR-mediated transrepressional and transactivational activity. Structural modification of 10 based on the reported X-ray crystal structure of the LXR more ..
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 Tested Compounds
 Tested Compounds
All(17)
 
 
Inactive(17)
 
 
 Tested Substances
 Tested Substances
All(17)
 
 
Inactive(17)
 
 
 Related BioAssays
 Related BioAssays
AID: 703192
Data Source: ChEMBL (863936)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-06-29
Modify Date: 2014-08-24

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Oxysterols receptor LXR-beta; AltName: Full=Liver X receptor beta; AltName: Full=Nuclear receptor NER; AltName: Full=Nuclear receptor subfamily 1 group H member 2; AltName: Full=Ubiquitously-expressed nuclear receptor
Description ..   
Protein Family: The ligand binding domain of Liver X receptors, a family of nuclear receptors of ligand-activated transcription factors
Comment ..   

Gene:NR1H2     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Design, synthesis, and biological evaluation of novel transrepression-selective liver X receptor (LXR) ligands with 5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one skeleton.

Abstract: To obtain novel transrepression-selective liver X receptor (LXR) ligands, we adopted a strategy of reducing the transactivational agonistic activity of the 5,11-dihydro-5-methyl-11-methylene-6H-dibenz[b,e]azepin-6-one derivative 10, which exhibits LXR-mediated transrepressional and transactivational activity. Structural modification of 10 based on the reported X-ray crystal structure of the LXR ligand-binding domain led to a series of compounds, of which almost all exhibited transrepressional activity at 1 or 10 muM but showed no transactivational activity even at 30 muM. Among the compounds obtained, 18 and 22 were confirmed to have LXR-dependent transrepressional activity by using peritoneal macrophages from wild-type and LXR-null mice. A newly developed fluorescence polarization assay indicated that they bind directly to LXRalpha. Next, further structural modification was performed with the guidance of docking simulations with LXRalpha, focusing on enhancing the binding of the ligands with LXRalpha through the introduction of substituents or heteroatom(s). Among the compounds synthesized, compound 48, bearing a hydroxyl group, showed potent, selective, and dose-dependent transrepressional activity.
(PMID: 22873709)
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: ADME
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Assay Cell Type: HEK293
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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