ArticleScience signaling2016
Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 92 citations in OpenAlex.
- Selective non-nuclear estrogen receptor activation with PaPE-1 evokes neuroprotection involving mTOR/MEK in an in vitro model of hypoxic/ischemic injury.Pharmacological reports : PR · 2026Article
- Estrogen Receptors and Enzymes Involved in Estrogen Synthesis as Breast Cancer Treatment Targets.International journal of molecular sciences · 2026Review
- Estren prevents beta-amyloid-induced basal forebrain cholinergic loss and long-term spatial memory deficits in aged female mice.Scientific reports · 2026Article
- Membrane-initiated estrogen receptor-α signaling in osteoblasts is crucial for normal regulation of the cortical bone in female mice.Bone research · 2025Article
- Exploring the effects of estrogen deficiency and aging on organismal homeostasis during menopause.Nature aging · 2024Review
- Posttreatment with PaPE-1 Protects from Aβ-Induced Neurodegeneration Through Inhibiting the Expression of Alzheimer's Disease-Related Genes and Apoptosis Process That Involves Enhanced DNA Methylation of Specific Genes.Molecular neurobiology · 2024Article
- Interrogating Estrogen Signaling Pathways in Human ER-Positive Breast Cancer Cells Forming Bone Metastases in Mice.Endocrinology · 2024Article
- The interaction of BDNF with estrogen in the development of hypertension and obesity, particularly during menopause.Frontiers in endocrinology · 2024Review
- Peering into the Brain's Estrogen Receptors: PET Tracers for Visualization of Nuclear and Extranuclear Estrogen Receptors in Brain Disorders.Biomolecules · 2023Article
- The EstroGene Database Reveals Diverse Temporal, Context-Dependent, and Bidirectional Estrogen Receptor Regulomes in Breast Cancer.Cancer research · 2023Article
- The G protein-coupled oestrogen receptor GPER in health and disease: an update.Nature reviews. Endocrinology · 2023Review
- A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer.International journal of molecular sciences · 2023Review
- Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies.International journal of molecular sciences · 2023Review
- The different natural estrogens promote endothelial healing through distinct cell targets.JCI insight · 2023Article
- EstroGene database reveals diverse temporal, context-dependent and directional estrogen receptor regulomes in breast cancer.bioRxiv : the preprint server for biology · 2023Article
- 17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice.American journal of physiology. Endocrinology and metabolism · 2023Article
- Membrane estrogen receptor-α contributes to female protection against high-fat diet-induced metabolic disorders.Frontiers in endocrinology · 2023Article
- Tie2-Cre-Induced Inactivation of Non-Nuclear Estrogen Receptor-α Signaling Abrogates Estrogen Protection Against Vascular Injury.JACC. Basic to translational science · 2023Article
- The emerging role of estrogen's non-nuclear signaling in the cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.Endocrine reviews · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
There is great medical need for estrogens with favorable pharmacological profiles that support desirable activities for menopausal women, such as metabolic and vascular protection, but that lack stimulatory activities on the breast and uterus. We report the development of structurally novel estrogens that preferentially activate a subset of estrogen receptor (ER) signaling pathways and result in favorable target tissue-selective activity. Through a process of structural alteration of estrogenic ligands that was designed to preserve their essential chemical and physical features but greatly reduced their binding affinity for ERs, we obtained "pathway preferential estrogens" (PaPEs), which interacted with ERs to activate the extranuclear-initiated signaling pathway preferentially over the nuclear-initiated pathway. PaPEs elicited a pattern of gene regulation and cellular and biological processes that did not stimulate reproductive and mammary tissues or breast cancer cells. However, in ovariectomized mice, PaPEs triggered beneficial responses both in metabolic tissues (adipose tissue and liver) that reduced body weight gain and fat accumulation and in the vasculature that accelerated repair of endothelial damage. This process of designed ligand structure alteration represents a novel approach to develop ligands that shift the balance in ER-mediated extranuclear and nuclear pathways to obtain tissue-selective, non-nuclear PaPEs, which may be beneficial for postmenopausal hormone replacement. The approach may also have broad applicability for other members of the nuclear hormone receptor superfamily.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.