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Antileishmanial activity of the estrogen receptor modulator raloxifene.

BACKGROUND: The treatment of leishmaniasis relies mostly on parenteral drugs with potentially serious adverse effects. Additionally, parasit … e burden. CONCLUSIONS/SIGNIFICANCE: The results of this work extend the investigation of selective estrogen receptor modulators as potential candidates for leishmaniasis treatment. The antileishmanial activity of raloxifene was demonstrated in vitro and in vivo. Raloxifene produces functional disorder on the plasma membrane of L. amazonensis promastigotes and leads to functi …

Modulation of transcriptional sensitivity of mineralocorticoid and estrogen receptors.

Recent reports describe the ability of factors to modulate the position of the dose-response curve of receptor-agonist complexes, and the amount of partial agonist activity of receptor-antagonist complexes, of androgen, glucocorticoid (GRs), and progesterone receptors (PRs). We now ask whether this modulation extends to the two remaining steroid receptors: mineralocorticoid (MRs) and estrogen receptors (ERs). These studies of MR were facilitated by our discovery that the antiglucocorticoid dexamethasone 21-mesylate (Dex-Mes) is a new antimineralocorticoid with significant amounts of partial ag

Raloxifene, a new selective estrogen receptor modulator.

There is evidence from observational studies that estrogen replacement therapy in postmenopausal women can reduce the rates of morbidity and mortality of atherosclerotic heart disease. The mechanism of this cardiovascular protective effect is not yet established, but favorable actions of hormone therapy on plasma lipids and vascular endothelial function have been proposed. Estrogens can also increase the risk of breast and uterine carcinoma. The new selective estrogen receptor modulator (SERM) raloxifene appears to have benefits similar to estrogen on plasma lipids and osteoporosis, but it doe

Structural modulation of oxidative metabolism in design of improved benzothiophene selective estrogen receptor modulators.

Raloxifene and arzoxifene are benzothiophene selective estrogen receptor modulators (SERMs) of clinical use in postmenopausal osteoporosis and treatment of breast cancer and potentially in hormone replacement therapy. The benefits of arzoxifene are attributed to improved bioavailability over raloxifene, whereas the arzoxifene metabolite, desmethylarzoxifene (DMA) is a more potent antiestrogen. As polyaromatic phenolics, benzothiophene SERMs undergo oxidative metabolism to electrophilic quinoids. The long-term clinical use of SERMs demands increased understanding of correlations between structu…

The role of selective estrogen receptor modulators on breast cancer: from tamoxifen to raloxifene.

The link between hormones and breast cancer growth and development has been recognized for more than a century. Estrogen stimulates the prol … hat work by virtue of their interaction with the ER; these drugs have come to be known as selective estrogen receptor modulators (SERMs). Tamoxifen, a SERM, emerged as the first antiestrogenic agent that is clinically applicable to breast cancer. Tamoxifen became the "gold standard" and established the principles of tumor targeting and identified the appropriate treatment str …

Synthesis and pharmacology of conformationally restricted raloxifene analogues: highly potent selective estrogen receptor modulators.

The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator (SERM) which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. In vivo structure-activity relationships and molecular modeling studies have indicated that the orientation of the basic amine-containing side chain of 1, relative to the stilbene plane, is an important discriminating factor for the maintenance of tissue selectivity. We have constructed a series of analogues of 1 in which this side chain is held in an orientation which is orthogonal to the stilben

Comparison of estrogens and selective estrogen receptor modulators (SERMs) used for menopausal hormone therapy.

A variety of natural and synthetic steroidal estrogens, as well as selective estrogen receptor modulators (SERMs), are used for menopausal hormone therapy (MHT) by oral and/or parenteral routes of administration. Two of the most widely used estrogens for MHT are conjugated equine estrogens (CEE) and estradiol (E2); other estrogens include esterified estrogens, piperazine estrone sulfate, estriol, estetrol (E4), E2 valerate, and ethinyl estradiol. Commonly used SERMs include tamoxifen, raloxifene, ospemifene, lasofoxifene, and bazedoxifene. These agents vary widely in their affinities for the e…

Изменение баланса иммунитета: формирующаяся роль селективных модуляторов рецепторов эстрогена в иммунитете и автоматическом иммунитете.

Селективные модуляторы рецепторов эстрогенов (SERM) представляют собой специфические для тканей и контекста регуляторы сигнала эстрогенных рецепторов (ER), первоначально разработанные для лечения рака груди и остеопороза. Растущее признание роли ERα и ERβ в модуляции развития иммунных клеток, терпимости, воспаления и противовирусной защиты привело к росту интереса к ERM как к потенциальной терапии аутоиммунных заболеваний. В настоящем обзоре резюмируются текущие механистические, предклинические и клинические данные о СЕРМ и связанных с ними ОВП агентах в аутоиммунных и иммунных условиях. Докли

Совпадение в аннотации оригинала
Selective estrogen receptor modulators (SERMs) are tissue- and context-specific regulators of estrogen receptor (ER) signaling, originally developed to treat breast cancer and osteoporosis. Increasing recognition of the roles of ERα and ERβ in modulation of immune cell development, tolerance, inflammation and antiviral defense has led to growing interest in …

An update on selective estrogen receptor modulators for the prevention and treatment of osteoporosis.

Several selective estrogen receptor modulators are in clinical development for postmenopausal osteoporosis. Bazedoxifene has shown significant reductions in vertebral and non-vertebral (in higher-risk women) fracture risk, with no evidence of breast or endometrial stimulation. Lasofoxifene has demonstrated significant reductions in vertebral and non-vertebral fracture risk, but has been associated with endometrial/uterine effects. Both selective estrogen receptor modulators were generally safe and well tolerated but have been associated with some "class effects" (e.g., hot flushes, venous thro…

Selective estrogen receptor modulators inhibit the effects of insulin-like growth factors in hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (HPT) predominantly affects perimenopausal women, leading to speculations that an estrogen imbalance may be liable. We have previously demonstrated the importance of the insulin-like growth factor (IGF) axis in HPT. Because the antiestrogen tamoxifen has been shown to modulate the IGF axis, we examined the interactions of selective estrogen receptor modulators (SERMs) and IGF in HPT. METHODS; Estrogen receptors were evaluated by Western immunoligand blotting. Sixteen parathyroid glands from 19 patients were included. After adhesion, the cells were treate…

The role of selective estrogen receptor modulators in the prevention and treatment of osteoporosis.

Osteoporosis can affect almost everyone in the population, and although clinical outcome of fracture is manifested in late life, the disease process begins in the early postmenopausal years in women. The pharmacologic agents currently available for osteoporosis prevention and treatment act by inhibiting bone resorption, and include estrogen or hormone replacement therapy (estrogen with progestin), bisphosphonates, salmon calcitonin nasal spray, and selective estrogen receptor modulators (SERMs). Raloxifene is a benzothiophene SERM that has estrogen against effects in bone and on serum lipid me…

Selective reduction of estrogen receptor (ER) positive breast cancer occurrence by estrogen receptor modulators supports etiological distinction between ER positive and ER negative breast cancers.

Reports that selective estrogen receptor modulators (SERMs) reduce occurrence of only estrogen receptor (ER) positive tumors strongly support the etiological distinction between ER positive and ER negative breast cancers. Based on these evidences three concepts are described: Concept I. The occurrence of ER negative tumor cells might be a consequence of the clonal selection among tumor cells. This would lead to mosaicism in the ER expression. If ER negative cells become the most prevalent clone, the patient will be diagnosed to have an ER negative breast cancer. Since all cancers start as ER p…

Selective Estrogen Receptor Degraders Induce Bradycardia by Modulating Nuclear Estrogen Signaling.

Selective estrogen receptor degraders (SERDs) are emerging therapies for estrogen receptor-positive (ER+) breast cancer. However, certain oral SERDs, including giredestrant and camizestrant, have been associated with bradycardia in clinical trials. To elucidate the underlying molecular mechanism, we used chemical biology and genetic approaches in a zebrafish model of SERD-induced bradycardia. Giredestrant and camizestrant induced significant bradycardia in wild-type zebrafish embryos, whereas fulvestrant and amcenestrant (SERDs that do not induce bradycardia in patients) did not alter heart ra

[Association of estrogens and selective estrogens receptors modulators: towards a renewal of the hormonal treatment?].

The life expectancy of women has risen in the past century from 48years to more than 80. The decline of endogenous estrogen production (in p … we will describe a new strategy of hormone therapy for menopause, combining estrogens and selective estrogen receptor modulators (SERM). We review the scientific underpinnings of this strategy, which may enable the renewal of hormone therapy for menopause.

The rise of selective estrogen receptor modulators (SERMs) in breast cancer therapy: a promising horizon.

Despite advancements in breast cancer treatment, breast cancer is still among the major causes of cancer-related deaths worldwide, with most breast cancers being estrogen receptor positive (ER+). Selective estrogen receptor modulators (SERMs) have been the core drug class used in endocrine therapy for ER+ breast cancer through tissue-specific conformational changes to the estrogen receptor. The present study critically evaluates the pharmacologic development, thermodynamics, and clinical effectiveness of SERMs. We systematically analyze approved agents (e.g., tamoxifen, raloxifene, bazedoxifen…

[Efficacy and safety of selective estrogen receptor modulators in patients with advanced chronic kidney disease].

Selective estrogen receptor modulators(SERMs)have beneficial effects on the improvement of bone mineral density of the spine and hip, and decrease the vertebral fracture in postmenopausal women. Similar to patients with advanced chronic kidney disease, including dialysis patients, however, SERMs cannot decrease the risk of hip fracture, which is extremely high in Japanese dialysis patients. One of the most important disadvantages of SERMs is an increase in the risk of venous thromboembolic events and fatal stroke in high-risk groups of the Framingham Stroke Risk Score. On the other hand, SERMs…

Gender difference in the neuroendocrine regulation of growth hormone axis by selective estrogen receptor modulators.

CONTEXT: In men, GH secretion is stimulated by estradiol derived locally from aromatization of testosterone. Recently, we showed that local estrogen also plays a major role in the central regulation of GH secretion in women. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs), drugs that block central estrogen action but exert estrogen-like effects in the liver, inhibiting hepatic IGF-I production. The relative impact of SERMs on the GH-IGF-I axis in men and women has not been investigated. OBJECTIVE: The aim of the study was to determine whether there is a gender diff…

Selective Estrogen Receptor Modulators (SERMs): Advances, Challenges, and Future Prospects in ER+ Breast Cancer Therapy.

Selective estrogen receptor modulators (SERMs) are an important class of drugs mainly useful in the treatment of breast cancer as they act as estrogen antagonists in the breast tissue but have an agonistic activity in bone and the cardiovascular system (CVS). ER-positive breast cancer, driven by estrogen signaling, is the most prevalent subtype worldwide. SERMs remain essential therapeutics, antagonizing estrogen activity in breast tissue while retaining agonist effects in bone and CVS. While traditional reviews have focused on triphenylethylene and benzothiophene scaffolds, this review provid…

Role of astrocytes in the neuroprotective actions of 17β-estradiol and selective estrogen receptor modulators.

Neuroprotective actions of 17β-estradiol (estradiol) are in part mediated by direct actions on neurons. Astrocytes, which play an essential … is not free from peripheral risks, alternatives for the hormone have been explored. Some selective estrogen receptor modulators (SERMs), which are already in use in clinical practice for the treatment of breast cancer, osteoporosis or menopausal symptoms, exert similar actions to estradiol on astrocytes. Therefore, SERMs represent therapeutic alternatives to estradiol for th …