International Union of Basic and Clinical Pharmacology. XCVII. G Protein–Coupled Estrogen Receptor and Its Pharmacologic Modulators

Prossnitz, Eric R.; Arterburn, Jeffrey B.

doi:10.1124/pr.114.009712

Cited by 203 publications

(233 citation statements)

References 448 publications

(562 reference statements)

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“…To our knowledge, this is the first member of this class of molecules ever adopted as a potential lead compound. Overall, in the last years, several endogenous and exogenous compounds have been screened and their actual ability to bind to GPER determined (31,32,37,48). For instance, two benzopyrroloxazine derivatives, namely PBX1 and PBX2, demonstrated the ability to act as selective GPER antagonists (33).…”

Section: Endogenous and Exogenous Gper Ligand Binding Modesmentioning

confidence: 99%

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Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands

Rosano

Ponassi

Santolla

et al. 2015

AAPS J

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Abstract. Estrogens influence multiple physiological processes and are implicated in many diseases as well. Cellular responses to estrogens are mainly mediated by the estrogen receptors (ER)α and ERβ, which act as ligand-activated transcription factors. Recently, a member of the G proteincoupled receptor (GPCR) superfamily, namely GPER/GPR30, has been identified as a further mediator of estrogen signalling in different pathophysiological conditions, including cancer. Today, computational methods are commonly used in all areas of health science research. Among these methods, virtual ligand screening has become an established technique for hit discovery and optimization. The absence of an established three-dimensional structure of GPER promoted studies of structure-based drug design in order to build reliable molecular models of this receptor. Here, we discuss the results obtained through the structure-based virtual ligand screening for GPER, which allowed the identification and synthesis of different selective agonist and antagonist moieties. These compounds led significant advances in our understanding of the GPER function at the cellular, tissue, and organismal levels. In particular, selective GPER ligands were critical toward the evaluation of the role elicited by this receptor in several pathophysiological conditions, including cancer. Considering that structure-based approaches are fundamental in drug discovery, future research breakthroughs with the aid of computer-aided molecular design and chemobioinformatics could generate a new class of drugs that, acting through GPER, would be useful in a variety of diseases as well as in innovative anticancer strategies.

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Section: Endogenous and Exogenous Gper Ligand Binding Modesmentioning

confidence: 99%

“…In contrast, it has been demonstrated that some estrogens, phyto-xenoestrogens, and antiestrogens can bind to GPER, which then activates downstream transduction pathways (37). Structurally, GPER is composed by 375 amino acid residues arranged in a seven-helical bundle intramembrane fold that is typical for all GPCRs.…”

Section: Introductionmentioning

confidence: 99%

Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands

Rosano

Ponassi

Santolla

et al. 2015

AAPS J

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“…89 Xenoextrogens, phytoextrogens, selective estrogen receptor modulators, selective estrogen receptor downregulators (SERDs), and catecholestrogens can also bind to GPER-1. 40,90 Whether the same holds true for 7β-hydroxy-epiandrosterone, a metabolite of dehydroxy-epiandrosterone, remains to be confirmed at present. 91 The identification of synthetic small molecules that act as a GPER-1-selective agonist (G1), and antagonist (G15 and G36), has shed some light in this field.…”

Section: Gper-1mentioning

confidence: 96%

Estrogen Signaling in the Adrenal Cortex

et al. 2016

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“…Estrogen also has rapid actions not fully explained by activities of ER␣ or ER␤, such as intracellular Ca 2ϩ mobilization, cAMP production, and phosphorylation. The G protein-coupled estrogen receptor 1 (GPER/GPR30) is associated with many rapid, pregenomic effects of estrogen (3,4) and also genomic effects, including up-regulation of genes like c-fos (5) and cyclin A and D1 (6,7), and fatty acid synthase (8). Since its recognition as a GPCR sensitive to estrogen (9,10), GPER/GPR30 has received significant attention (4).…”

Section: Estrogen Exerts Many Effects On the Vascular Endothelium Camentioning

confidence: 99%

Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1

Tran

Firkins

Giles

et al. 2016

Journal of Biological Chemistry

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International Union of Basic and Clinical Pharmacology. XCVII. G Protein–Coupled Estrogen Receptor and Its Pharmacologic Modulators

Cited by 203 publications

References 448 publications

Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands

Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands

Estrogen Signaling in the Adrenal Cortex

Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-coupled Estrogen Receptor 1

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