Estrogen Receptor α (ERα)-targeting Compounds and Derivatives: Recent Advances in Structural Modification and Bioactivity

2019 ◽  
Vol 19 (15) ◽  
pp. 1318-1337 ◽  
Author(s):  
Wei-Yun Guo ◽  
Shang-Ming-Zhu Zeng ◽  
Girdhar Singh Deora ◽  
Qing-Shan Li ◽  
Ban-Feng Ruan
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Side Effects ◽  
Structural Modification ◽  
Estrogen Therapy ◽  
Estrogen Receptor Α ◽  
The Past ◽  
Estrogen Receptor Modulators ◽  
Common Cancer ◽  
Receptor Modulators

Breast cancer is the most common cancer suffered by female, and the second highest cause of cancer-related death among women worldwide. At present, hormone therapy is still the main treatment route and can be divided into three main categories: selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs). However, breast cancer is difficult to cure even after several rounds of anti-estrogen therapy and most drugs have serious side-effects. Here, we review the literature published over the past five years regarding the isolation and synthesis of analogs and their derivatives.

scholarly journals Ligand-Selective Interdomain Conformations of Estrogen Receptor-α

2007 ◽  
Vol 21 (1) ◽  
pp. 49-61 ◽  
Author(s):  
Adrian Padron ◽  
Li Li ◽  
Eric M. Kofoed ◽  
Fred Schaufele
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Energy Transfer ◽  
Hormone Replacement ◽  
Estrogen Receptor Α ◽  
Full Length ◽  
Estrogen Receptor Modulators ◽  
Interaction Kinetics ◽  
Receptor Modulators

Abstract Selective estrogen receptor modulators (SERMs) inhibit estrogen activation of the estrogen receptor (ER) in some tissues but activate ER in other tissues. These tissue-selective actions suggest that SERMs may be identified with tissue specificities that would improve the safety of breast cancer and hormone replacement therapies. The identification of an improved SERM would be aided by understanding the effects of each SERM on the structure and interactions of ER. To date, the inability to obtain structures of the full-length ER has limited our structural characterization of SERM action to their antiestrogenic effects on the isolated ER ligand binding domain. We studied the effects of estradiol and the clinically useful SERMs 4-hydroxytamoxifen and fulvestrant on the conformation of the full-length ERα dimer complex by comparing, in living human breast cancer cells, the amounts of energy transfer between fluorophores attached to different domains of ERα. Estradiol, 4-hydroxytamoxifen, and fulvestrant all promoted the rapid formation of ERα dimers with equivalent interaction kinetics. The amino- and carboxyl-terminal ERα domains both contain activation functions differentially affected by these ligands, but the positions of only the carboxyl termini differed upon binding with estradiol, 4-hydroxytamoxifen, or fulvestrant. The association of a specific ERα dimer conformation with the binding of ligands of different clinical effect will assist the identification of a SERM with optimal tissue-selective estrogenic and antiestrogenic activities. These studies also provide a roadmap for dissecting important structural and kinetic details for any protein complex from the quantitative analysis of energy transfer.

scholarly journals Design and Synthesis of Novel Chalcone-Phenylpyranone Derivatives as Estrogen Receptor Modulators

Proceedings ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 30
Author(s):  
Pritam N. Dube ◽  
Yogita B. Thombare ◽  
Vivekanand A. Chatpalliwar
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Docking Study ◽  
Estrogen Receptor Α ◽  
Side Chain ◽  
Design And Synthesis ◽  
Estrogen Receptor Modulators ◽  
Receptor Modulators ◽  
Mcf 7

Selective estrogen receptor modulators (SERMs) are a class of drugs that act on the estrogen receptor (ER). SERMs are used for treatment and reduction of risk of breast cancer. Herewith we had designed, synthesized, and evaluated chalcone-phenylpyran-2-one derivatives bearing a N,N-dimethyl ethylamine side chain for their anti-breast cancer activity on MCF-7 and Zr-75-1 cell lines in-vitro. The pharmacological data indicated that most of tested compounds showed moderate to significant cytotoxicity and high selectivity toward the estrogen receptor. The Structure activity relationaship analyses indicated that compounds 5f with 2,6-dichloro substitution was more effective. Docking study was performed to predict binding orientation towards the estrogen receptor-α.

scholarly journals Incident Type 2 Diabetes Risk of Selective Estrogen Receptor Modulators in Female Patients with Breast Cancer

2021 ◽  
Vol 14 (9) ◽  
pp. 925
Author(s):  
Yeo-Jin Choi ◽  
Keunhyeong Bak ◽  
Yoon Yeo ◽  
Yongwon Choi ◽  
Sooyoung Shin
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Cancer ◽  
Selective Estrogen Receptor Modulators ◽  
Diabetes Risk ◽  
Incident Diabetes ◽  
Estrogen Receptor Modulators ◽  
Increase Diabetes Risk ◽  
Receptor Modulators

Accumulating evidence indicates a link between diabetes and cancer. Selective estrogen receptor modulators (SERMs) may increase diabetes risk via antiestrogen effects. This study investigated incident diabetes risk of SERM treatment and its effects on metastatic cancer and death prevention in breast cancer survivors. This retrospective cohort study included female patients with early-stage breast cancer, treated with or without SERMs, between 2008 and 2020 in a tertiary care hospital in Korea. Four propensity score-matched comparison pairs were designed: SERM use versus non-use, long-term use (≥1500 days) versus non-use, tamoxifen use versus non-use, and toremifene use versus non-use; then, logistic regression analysis was performed for risk analysis. SERMs in general were not associated with an elevated risk of diabetes; however, when used for ≥1500 days, SERMs—especially toremifene—substantially increased diabetes risk in breast cancer patients (OR 1.63, p = 0.048). Meanwhile, long-term SERM treatment was effective at preventing metastatic cancer (OR 0.20, p < 0.001) and death (OR 0.13, p < 0.001). SERM treatment, albeit generally safe and effective, may increase diabetes risk with its long-term use in women with breast cancer. Further studies are required to verify the association between toremifene treatment and incident diabetes.

scholarly journals Hormone therapy in menopausal women with fibroids: is it safe? (Literature review)

2019 ◽  
Vol 2 (14) ◽  
pp. 38-44
Author(s):  
Ya. Z. Zaydieva
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Hormone Therapy ◽  
Literature Search ◽  
Effective Treatment Option ◽  
Estrogen Receptor Modulators ◽  
Increased Risk ◽  
Menopausal Women ◽  
Receptor Modulators ◽  
Higher Doses

Hormone therapy is an effective treatment option for menopausal women, although prolonged use of hormone therapy is associated with a slightly increased risk of breast cancer, thromboembolism, and stroke. A literature search for studies evaluating the effects of hormone therapy in menopausal women with asymptomatic fibroids demonstrated variable effects of hormone therapy on the volume and size of the fibroids. Some studies have demonstrated an increase in size of pre-existing asymptomatic fibroids and formation of new fibroids with higher doses of progestogen in combination therapy. Selective estrogen receptor modulators having tissue-specific estrogen agonistic and antagonistic actions such as raloxifene have a favorable clinical profile and may be better alternatives in women with asymptomatic fibroids.

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