scholarly journals Antagonists for Constitutively Active Mutant Estrogen Receptors: Insights into the Roles of Antiestrogen-Core and Side-Chain

2018 ◽  
Vol 13 (12) ◽  
pp. 3374-3384 ◽  
Author(s):  
Abhishek Sharma ◽  
Weiyi Toy ◽  
Valeria Sanabria Guillen ◽  
Naina Sharma ◽  
Jian Min ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Side Chain ◽  
Constitutively Active

Novel Carbamοyloxy Analogues of Tamoxifen: Synthesis, Molecular Docking and Bioactivity Evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Konstantinos M. Kasiotis ◽  
George Lambrinidis ◽  
Nikolas Fokialakis ◽  
Serkos A. Haroutounian
Keyword(s):  
Estrogen Receptors ◽  
Theoretical Calculations ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Endocrine Treatment ◽  
Side Chain ◽  
Binding Affinities ◽  
Correlation Pattern ◽  
One Pot ◽  
Structure Activity

Background: Tamoxifen (TAM), a non-steroidal antiestrogen, constitutes the endocrine treatment of choice against breast cancer. Since its inauguration, substantial effort has been devoted towards the design and synthesis of TAM’s analogues aiming to improve its bioactivity and reveal their structure-activity relationship. Objective: One of the most studied synthetic features of TAM’s structure is the ether side chain, which is strongly related to its positioning into the active site of the Estrogen Receptors (ERα and ERβ). Herein, we present the application of a straightforward route for the efficient synthesis of selected novel carbamoyloxy analogues of TAM and the evaluation of their respective binding affinities to the Estrogen Receptors α and β. Method: A one-pot reaction was applied for the construction of TAM’s triarylethylene core moiety, which subsequently was derivatized to provide efficiently the target carbamoyloxy analogues of TAM. The Z and E isomers of the latter were separated using RP-HPLC-UV and their binding affinities to ERα and ERβ were measured. Results and Discussion: Among all compounds synthesized, the dimethyl derivative was determined as the most potent for both receptors, displaying binding affinity values comparable to TAM, though the Z-diethyl analogue maintained substantial affinity to both ERs. The aforementioned results were further studied by theoretical calculations and molecular modelling to delineate a concordance among calculations and biological activity. Conclusion: Approach applied herein permitted the extraction of a useful structure-activity relationship correlation pattern highlighting the importance of a chemically stabilized tamoxifen side chain.

scholarly journals Structurally Novel Antiestrogens Elicit Differential Responses from Constitutively Active Mutant Estrogen Receptors in Breast Cancer Cells and Tumors

2017 ◽  
Vol 77 (20) ◽  
pp. 5602-5613 ◽  
Author(s):  
Yuechao Zhao ◽  
Mary J. Laws ◽  
Valeria Sanabria Guillen ◽  
Yvonne Ziegler ◽  
Jian Min ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptors ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Differential Responses ◽  
Constitutively Active

Subtle Side-Chain Modifications of the Hop Phytoestrogen 8-Prenylnaringenin Result in Distinct Agonist/Antagonist Activity Profiles for Estrogen Receptors α and β

2006 ◽  
Vol 49 (25) ◽  
pp. 7357-7365 ◽  
Author(s):  
Frederik Roelens ◽  
Nina Heldring ◽  
Willem Dhooge ◽  
Martin Bengtsson ◽  
Frank Comhaire ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Side Chain ◽  
Antagonist Activity

Constitutively active phosphatidlyinositol 3-kinase (Pl 3-K) and Akt are sufficient to stimulate NHE3: Insights in mechanisms of NHE3 stimulation

2001 ◽  
Vol 120 (5) ◽  
pp. A696-A696
Author(s):  
W KWON ◽  
D JOHNS ◽  
M CAVET ◽  
J PARK ◽  
P TSICHLIS ◽  
...  
Keyword(s):  
Constitutively Active

Antibodies directed against retained intron 4 of the constitutively active CCK-2 receptor bind to a tumour-specific epitope

2001 ◽  
Vol 120 (5) ◽  
pp. A496-A496 ◽  
Author(s):  
P CLARKE ◽  
S GRIMES ◽  
D MCWILLIAMS ◽  
W KLEIE ◽  
K KHAN ◽  
...  
Keyword(s):  
Specific Epitope ◽  
Retained Intron ◽  
Intron 4 ◽  
Constitutively Active

Electroluminescent properties of side-chain naphthalimide-derivated polymers

1998 ◽  
Vol 95 (6) ◽  
pp. 1351-1354 ◽  
Author(s):  
C.-M. Bouché ◽  
P. Le Barny ◽  
H. Facoetti ◽  
F. Soyer ◽  
P. Robin
Keyword(s):  
Side Chain
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