17720-60-4Relevant articles and documents
Structure–activity relationship of phytoestrogen analogs as ERα/β agonists with neuroprotective activities
Cho, Hye Won,Gim, Hyo Jin,Li, Hua,Subedi, Lalita,Kim, Sun Yeou,Ryu, Jae-Ha,Jeon, Raok
, p. 99 - 105 (2021/01/06)
A set of isoflavononid and flavonoid analogs was prepared and evaluated for estrogen receptor α (ERα) and ERβ transactivation and anti-neuroinflammatory activities. Structure–activity relationship (SAR) study of naturally occurring phytoestrogens, their metabolites, and related isoflavone analogs revealed the importance of the C-ring of isoflavonoids for ER activity and selectivity. Docking study suggested putative binding modes of daidzein 2 and dehydroequol 8 in the active site of ERα and ERβ, and provided an understanding of the promising activity and selectivity of dehydroequol 8. Among the tested compounds, equol 7 and dehydroequol 8 were the most potent ERα/β agonists with ERβ selectivity and neuroprotective activity. This study provides knowledge on the SAR of isoflavonoids for further development of potent and selective ER agonists with neuroprotective potential.
Identification of an Orally Bioavailable Chromene-Based Selective Estrogen Receptor Degrader (SERD) That Demonstrates Robust Activity in a Model of Tamoxifen-Resistant Breast Cancer
Nagasawa, Johnny,Govek, Steven,Kahraman, Mehmet,Lai, Andiliy,Bonnefous, Celine,Douglas, Karensa,Sensintaffar, John,Lu, Nhin,Lee, Kyoungjin,Aparicio, Anna,Kaufman, Josh,Qian, Jing,Shao, Gang,Prudente, Rene,Joseph, James D.,Darimont, Beatrice,Brigham, Daniel,Maheu, Kate,Heyman, Richard,Rix, Peter J.,Hager, Jeffrey H.,Smith, Nicholas D.
supporting information, p. 7917 - 7928 (2018/09/06)
About 75% of breast cancers are estrogen receptor alpha (ER-α) positive, and women typically initially respond well to antihormonal therapies such as tamoxifen and aromatase inhibitors, but resistance often emerges. Fulvestrant is a steroid-based, selective estrogen receptor degrader (SERD) that both antagonizes and degrades ER-α and shows some activity in patients who have progressed on antihormonal agents. However, fulvestrant must be administered by intramuscular injections that limit its efficacy. We describe the optimization of ER-α degradation efficacy of a chromene series of ER modulators resulting in highly potent and efficacious SERDs such as 14n. When examined in a xenograft model of tamoxifen-resistant breast cancer, 14n (ER-α degradation efficacy = 91%) demonstrated robust activity, while, despite superior oral exposure, 15g (ER-α degradation efficacy = 82%) was essentially inactive. This result suggests that optimizing ER-α degradation efficacy in the MCF-7 cell line leads to compounds with robust effects in models of tamoxifen-resistant breast cancer derived from an MCF-7 background.
TREATMENT OF HOT FLUSHES, VASOMOTOR SYMPTOMS, AND NIGHT SWEATS WITH SEX STEROID PRECURSORS IN COMBINATION WITH SELECTIVE ESTROGEN RECEPTOR MODULATORS
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Paragraph 0142, (2017/08/01)
Novel methods for reduction or elimination of the incidence of hot flushes, vasomotor symptoms, and night sweats while decreasing the risk of acquiring breast, uterine or endometrial cancer and furthermore having beneficial effect by inhibiting the develo