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BioAssay: AID 728187

Displacement of [3H]E2 from human recombinant ERbeta receptor after overnight incubation by liquid scintillation counting analysis relative to 17beta-estradiol

Estrogen receptor (ER) antagonists are valuable in the treatment of ER-positive human breast cancer. In this study, we designed and synthesized nine new derivatives of 17beta-estradiol (E2) with a bulky side chain attached to its C-7alpha position, and determined their ER antagonistic activity using in vitro bioassays. Four of the derivatives showed a strong inhibition of ERalpha transactivation more ..
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 Tested Compounds
 Tested Compounds
All(9)
 
 
Unspecified(9)
 
 
 Tested Substances
 Tested Substances
All(9)
 
 
Unspecified(9)
 
 
 Related BioAssays
 Related BioAssays
AID: 728187
Data Source: ChEMBL (940753)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2013-11-07
Modify Date: 2014-05-27

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Steroid hormone receptor ERR2; AltName: Full=ERR beta-2; AltName: Full=Estrogen receptor-like 2; AltName: Full=Estrogen-related receptor beta; Short=ERR-beta; AltName: Full=Nuclear receptor subfamily 3 group B member 2
Description ..   
Protein Family: The ligand binding domain of estrogen receptor-related nuclear receptors
Comment ..   

Gene:ESRRB     Related Protein 3D Structures     More BioActivity Data..
Tested Compounds:
Description:
Title: Synthesis of novel estrogen receptor antagonists using metal-catalyzed coupling reactions and characterization of their biological activity.

Abstract: Estrogen receptor (ER) antagonists are valuable in the treatment of ER-positive human breast cancer. In this study, we designed and synthesized nine new derivatives of 17beta-estradiol (E2) with a bulky side chain attached to its C-7alpha position, and determined their ER antagonistic activity using in vitro bioassays. Four of the derivatives showed a strong inhibition of ERalpha transactivation activity in a luciferase reporter assay and blocked ERalpha interactions with coactivators. Similarly, these derivatives also strongly inhibited the growth of the ERalpha-positive human breast cancer cells. Computational docking analysis was conducted to model the interaction of these antagonists with the human ERalpha and showed that they could tightly bind to the ERalpha in a manner similar to that of ICI-182,780, a pure ER antagonist. These results provide an example that attachment of a bulky side chain to the C-7alpha position of E2 can produce ER antagonists with ER affinity comparable to that of ICI-182,780.
(PMID: 23448346)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1RBA activity commentRBA activity commentString
2RBA standard flagRBA standard flagInteger
3RBA qualifierRBA qualifierString
4RBA published valueRBA published valueFloat%
5RBA standard valueRBA standard valueFloat%

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