Antagonism of Estrogen Receptor α-Driven Transcription Mediated by AP-1 in Breast Cancer Therapy
Abstract
:1. Introduction
2. ERα-Mediated Transcriptions
3. Ligand Insertion within the ERα Binding Pocket
4. Assessing the Activity of 11β Substituted Estradiol Derivatives
4.1. Nature and Origin of the Investigated Compounds
4.2. Experimental Procedures
4.3. Results
4.3.1. Global View of Our Investigation
4.3.2. Small-Size 11β Substituents
4.3.3. 11β Side-Chains
SERMs
SERDs
5. Concluding Remarks
Supplementary Materials
Funding
Acknowledgments
Conflicts of Interest
References
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Binding | LxxLL Recruitment | Transcription | ERα Level | |||
---|---|---|---|---|---|---|
0 | 25 (°C) | ERE | AP-1 | |||
estradiol | 100 | 100 | 100/−7 | 100/−10 | 30/−6 | 60/−9 |
tamoxifen | 5 | 40 | −25/−6 | 25/−6 | 100/−6 | 500/−7 |
7a-fulvestrant | 10 | 100 | −40/−8 | 15/−6 | 80/−7 | 35/−7 |
A. Small-size substituents (estrogens) | ||||||
-CH3 | 100 | 250 | 100/−8 | 100/−11 | ? | 50/−9 |
-CH2Cl | 100 | 200 | 100/−8 | 100/−11 | ? | 40/−9 |
-CCH (ethynyl) | 30 | 170 | 100/−8 | 285/−11 | ? | 45/−9 |
B. Side-chain substituents (* estrogens, ** SERMs, *** SERDs) | ||||||
-C6H13 ** | 10 | 100 | −40/−7 | 65/−10 | 120/−7 | 225/−8 |
-C6F13 * | 3 | 3 | 15/−8 | 90/−6 | 55/−9 | 45/−9 |
-C2H4CF9 ** | 10 | 10 | −30/−7 | 30/−9 | 65/−8 | 140/−7 |
-(CH2)9-X *** | 6 | 80 | −40/−8 | 15/−6 | 125/−7 | 35/−7 |
-(CH2)3(CF2)4(CH2)2 -X *** | 2 | 10 | −40/−8 | 65/−6 | 110/−8 | 80/−6 |
X = -S(O)(CH3)3C2F5 |
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Leclercq, G. Antagonism of Estrogen Receptor α-Driven Transcription Mediated by AP-1 in Breast Cancer Therapy. Endocrines 2024, 5, 102-115. https://doi.org/10.3390/endocrines5010007
Leclercq G. Antagonism of Estrogen Receptor α-Driven Transcription Mediated by AP-1 in Breast Cancer Therapy. Endocrines. 2024; 5(1):102-115. https://doi.org/10.3390/endocrines5010007
Chicago/Turabian StyleLeclercq, Guy. 2024. "Antagonism of Estrogen Receptor α-Driven Transcription Mediated by AP-1 in Breast Cancer Therapy" Endocrines 5, no. 1: 102-115. https://doi.org/10.3390/endocrines5010007