Bookmark and Share
BioAssay: AID 438596

Displacement of [3H]9-cis-retinoic acid form human RXRalpha expressed in human Caco-2 cells after 16 hrs

This report describes the synthesis of analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (1), commonly known as bexarotene, and their analysis in acting as retinoid X receptor (RXR)-specific agonists. Compound 1 has FDA approval to treat cutaneous T-cell lymphoma (CTCL); however, its use can cause side effects such as hypothyroidism and increased more ..
_
   
 Tested Compounds
 Tested Compounds
All(4)
 
 
Active(4)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Active(4)
 
 
 Related BioAssays
 Related BioAssays
AID: 438596
Data Source: ChEMBL (589774)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-07-08
Modify Date: 2014-05-25

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Retinoic acid receptor RXR-alpha; AltName: Full=Nuclear receptor subfamily 2 group B member 1; AltName: Full=Retinoid X receptor alpha
Description ..   
Protein Family: The ligand binding domain of the retinoid X receptor and Ultraspiracle, members of nuclear receptor superfamily
Comment ..   

Gene:RXRA     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 4
Description:
Title: Modeling, synthesis and biological evaluation of potential retinoid X receptor (RXR) selective agonists: novel analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene).

Abstract: This report describes the synthesis of analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (1), commonly known as bexarotene, and their analysis in acting as retinoid X receptor (RXR)-specific agonists. Compound 1 has FDA approval to treat cutaneous T-cell lymphoma (CTCL); however, its use can cause side effects such as hypothyroidism and increased triglyceride concentrations, presumably by disruption of RXR heterodimerization with other nuclear receptors. The novel analogues in the present study have been evaluated for RXR activation in an RXR mammalian-2-hybrid assay as well as an RXRE-mediated transcriptional assay and for their ability to induce apoptosis as well as for their mutagenicity and cytotoxicity. Analysis of 11 novel compounds revealed the discovery of three analogues that best induce RXR-mediated transcriptional activity, stimulate apoptosis, have comparable K(i) and EC(50) values to 1, and are selective RXR agonists. Our experimental approach suggests that rational drug design can develop new rexinoids with improved biological properties.
(PMID: 19791803)
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: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Assay Cell Type: Caco-2

Target Type: Target is a single protein chain

Result Definitions
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6Ki activity commentKi activity commentString
7Ki standard flagKi standard flagInteger
8Ki qualifierKi qualifierString
9Ki published valueKi published valueFloatnM
10Ki standard valueKi standard valueFloatnM
11Ki binding domainsKi binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
PageFrom: