Bookmark and Share
BioAssay: AID 728189

Displacement of [3H]E2 from human recombinant ERbeta receptor after overnight incubation by liquid scintillation counting analysis

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 ..
_
   
 Tested Compounds
 Tested Compounds
All(10)
 
 
Active(10)
 
 
 Tested Substances
 Tested Substances
All(10)
 
 
Active(10)
 
 
 Related BioAssays
 Related BioAssays
AID: 728189
Data Source: ChEMBL (940755)
Depositor Category: Literature, Extracted
Deposit Date: 2013-11-07

Data Table ( Complete ):           Active    All
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..
BioActive Compounds: 10
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)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 11254

ChEMBL Target Type: Target is a single protein chain

Result Definitions
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloatnM
10IC50 standard valueIC50 standard valueFloatnM
11IC50 binding domainsIC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
PageFrom: