Enhanced estrogen receptor beta (ERβ) selectivity of fluorinated carborane-containing ER modulators

Ohta, Kiminori; Ogawa, Tokuo; Kaise, Asako; Endo, Yasuyuki

doi:10.1016/j.bmcl.2013.10.067

Cited by 26 publications

(17 citation statements)

References 26 publications

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“…Furthermore, C,C′ -difluoro- p -carboranyl phenol 43 (Fig. 9) was reported to have a higher beta selectivity (10-fold), though a lower binding affinity (ERβ-RBA = 50%) than 42 [119]. …”

Section: Update On Chemical Classes Comprising Erα and Erβ Modulatorsmentioning

confidence: 99%

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

et al. 2014

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Estrogen receptors alpha (ERα) and beta (ERβ) are nuclear transcription factors that are involved in the regulation of many complex physiological processes in humans. Modulation of these receptors by prospective therapeutic agents is currently being considered for prevention and treatment of a wide variety of pathological conditions, such as, cancer, metabolic and cardiovascular diseases, neurodegeneration, inflammation, and osteoporosis. This review provides an overview and update of compounds that have been recently reported as modulators of ERs, with a particular focus on their potential clinical applications.

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“…Furthermore, C,C′ -difluoro- p -carboranyl phenol 43 (Fig. 9) was reported to have a higher beta selectivity (10-fold), though a lower binding affinity (ERβ-RBA = 50%) than 42 [119]. …”

Section: Update On Chemical Classes Comprising Erα and Erβ Modulatorsmentioning

confidence: 99%

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

et al. 2014

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“…Compound 38 ( Figure 15 ) in this series displayed 8.5-fold greater selectivity for ERβ. Therefore, introduction of a fluorine atom at the 9-position of the m-carborane cage reduced the ERα binding affinity [ 85 ].…”

Section: Carborane Analoguesmentioning

confidence: 99%

Estrogen Receptor Ligands: A Review (2013–2015)

Farzaneh

Zarghi

2016

Sci. Pharm.

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Estrogen receptors (ERs) are a group of compounds named for their importance in both menstrual and estrous reproductive cycles. They are involved in the regulation of various processes ranging from tissue growth maintenance to reproduction. Their action is mediated through ER nuclear receptors. Two subtypes of the estrogen receptor, ERα and ERβ, exist and exhibit distinct cellular and tissue distribution patterns. In humans, both receptor subtypes are expressed in many cells and tissues, and they control key physiological functions in various organ systems. Estrogens attract great attention due to their wide applications in female reproductive functions and treatment of some estrogen-dependent cancers and osteoporosis. This paper provides a general review of ER ligands published in international journals patented between 2013 and 2015. The broad physiological profile of estrogens has attracted the attention of many researchers to develop new estrogen ligands as therapeutic molecules for various clinical purposes. After the discovery of the ERβ receptor, subtype-selective ligands could be used to elicit beneficial estrogen-like activities and reduce adverse side effects, based on the different distributions and relative levels of the two ER subtypes in different estrogen target tissues. Therefore, recent literature has focused on selective estrogen ligands as highly promising agents for the treatment of some types of cancer, as well as for cardiovascular, inflammatory, and neurodegenerative diseases. Estrogen receptors are nuclear transcription factors that are involved in the regulation of many complex physiological functions in humans. Selective estrogen ligands are highly promising targets for treatment of some types of cancer, as well as for cardiovascular, inflammatory and neurodegenerative diseases. Extensive structure-activity relationship studies of ER ligands based on small molecules indicate that many different structural scaffolds may provide high-affinity compounds, provided that some basic structural requirements are present.

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“…Ohta et al explored carborane-containing compounds in terms of their ERβ specificity through substitution with fluorine [ 126 ] (compounds 14 and 15 ) and aliphatic groups [ 127 ] (compound 16 ). In the first study, fluorinated carboranyl phenol was investigated for ERβ selectivity, whereby the addition of a fluorine atom was found to increase the ERβ selectivity compared to non-fluorinated compounds in the series.…”

Section: Updated Overview Of Subtype Selective Compoundsmentioning

confidence: 99%

“…The selectivity of these compounds was suggested to result from repulsion with M421 of ERα (I373 in ERβ). Both compounds showed ER agonistic activities, albeit weaker than endogenous E2 [ 126 ]. Compounds 14 and 15 were also tested in MCF-7 assay where both compounds were found to promote cell proliferation in a dose-dependent manner, although as weaker agonists than E2.…”

Section: Updated Overview Of Subtype Selective Compoundsmentioning

confidence: 99%

Versatility or Promiscuity: The Estrogen Receptors, Control of Ligand Selectivity and an Update on Subtype Selective Ligands

Perkins

Tong

et al. 2014

IJERPH

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The estrogen receptors (ERs) are a group of versatile receptors. They regulate an enormity of processes starting in early life and continuing through sexual reproduction, development, and end of life. This review provides a background and structural perspective for the ERs as part of the nuclear receptor superfamily and discusses the ER versatility and promiscuity. The wide repertoire of ER actions is mediated mostly through ligand-activated transcription factors and many DNA response elements in most tissues and organs. Their versatility, however, comes with the drawback of promiscuous interactions with structurally diverse exogenous chemicals with potential for a wide range of adverse health outcomes. Even when interacting with endogenous hormones, ER actions can have adverse effects in disease progression. Finally, how nature controls ER specificity and how the subtle differences in receptor subtypes are exploited in pharmaceutical design to achieve binding specificity and subtype selectivity for desired biological response are discussed. The intent of this review is to complement the large body of literature with emphasis on most recent developments in selective ER ligands.

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Enhanced estrogen receptor beta (ERβ) selectivity of fluorinated carborane-containing ER modulators

Cited by 26 publications

References 26 publications

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ligands and clinical potential

Estrogen Receptor Ligands: A Review (2013–2015)

Versatility or Promiscuity: The Estrogen Receptors, Control of Ligand Selectivity and an Update on Subtype Selective Ligands

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