ArticleNPJ breast cancer2022
Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells.
Article in NPJ breast cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Selective estrogen receptor degraders and their effect on the breast cancer immune microenvironment.The Journal of clinical investigation · 2026Review
- Allosteric Induction of Estrogen Receptor Ligand Binding Domain Tetramerization by a Distinct Complete Estrogen Receptor Antagonist.ACS medicinal chemistry letters · 2026Article
- Targeting the ERα DBD-LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation.Molecular cancer therapeutics · 2026Article
- Biological and computer-aided evaluation of 3-methoxy-13α-estrone-16α-diphenylphosphine oxide as a new antiestrogenic agent.Scientific reports · 2025Article
- Article
- Benzestrol Isomer Stereochemistry Determines the Distinct Estrogenic Activities and Conformations of the Eight Isomers When Bound to Estrogen Receptor α.ACS pharmacology & translational science · 2025Article
- Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.Breast cancer research : BCR · 2025Article
- Review
- Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537SResearch square · 2024Article
- Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537SbioRxiv : the preprint server for biology · 2024Article
- Estrogen Receptor Alpha Mutations, Truncations, Heterodimers, and Therapies.Endocrinology · 2024Review
- Pharmacokinetic Analysis of [Molecular imaging and biology · 2024Article
- New generation estrogen receptor-targeted agents in breast cancer: present situation and future prospectives.Acta materia medica · 2024Article
- Editorial: Hormone resistance in cancer.Frontiers in endocrinology · 2023Article
- Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells.NPJ breast cancer · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Estrogen receptor alpha (ERα) is a ligand-dependent master transcriptional regulator and key driver of breast cancer pathology. Small molecule hormones and competitive antagonists favor unique ERα conformational ensembles that elicit ligand-specific transcriptional programs in breast cancer and other hormone-responsive tissues. By affecting disparate ligand binding domain structural features, unconventional ligand scaffolds can redirect ERα genomic binding patterns to engage novel therapeutic transcriptional programs. To improve our understanding of these ERα structure-transcriptional relationships, we develop a series of chemically unconventional antagonists based on the antiestrogens elacestrant and lasofoxifene. High-resolution x-ray co-crystal structures show that these molecules affect both classical and unique structural motifs within the ERα ligand binding pocket. They show moderately reduced antagonistic potencies on ERα genomic activities but are effective anti-proliferative agents in luminal breast cancer cells. Interestingly, they favor a 4-hydroxytamoxifen-like accumulation of ERα in breast cancer cells but lack uterotrophic activities in an endometrial cell line. Importantly, RNA sequencing shows that the lead molecules engage transcriptional pathways similar to the selective estrogen receptor degrader fulvestrant. This advance shows that fulvestrant-like genomic activities can be achieved without affecting ERα accumulation in breast cancer cells.
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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.