ArticleNature communications2018
Specific stereochemistry of OP-1074 disrupts estrogen receptor alpha helix 12 and confers pure antiestrogenic activity.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- Selective estrogen receptor degraders and their effect on the breast cancer immune microenvironment.The Journal of clinical investigation · 2026Review
- ESR1 mutations and CDK4/6 inhibitor choice shape clonal selection and adaptive cell states during acquired resistance.Genome medicine · 2026Article
- Allosteric Induction of Estrogen Receptor Ligand Binding Domain Tetramerization by a Distinct Complete Estrogen Receptor Antagonist.ACS medicinal chemistry letters · 2026Article
- A ternary switch model governing ERα ligand binding domain conformation.Nature communications · 2025Article
- Imlunestrant a next-generation oral SERD overcomes ESR1 mutant resistance in estrogen receptor-positive breast cancer.JCI insight · 2025Article
- Article
- Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.Breast cancer research : BCR · 2025Article
- Targeting Oestrogen Receptor Signalling in Breast Cancer Therapy.Advances in experimental medicine and biology · 2025Review
- 17β-Estradiol, through activating the G protein-coupled estrogen receptor, exacerbates the complication of benign prostatic hyperplasia in type 2 diabetes mellitus patients by inducing prostate proliferation.Journal of pharmaceutical analysis · 2024Article
- 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
- Palazestrant (OP-1250), A Complete Estrogen Receptor Antagonist, Inhibits Wild-type and Mutant ER-positive Breast Cancer Models as Monotherapy and in Combination.Molecular cancer therapeutics · 2024Article
- ESR1 activating mutations: From structure to clinical application.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Unconventional isoquinoline-based SERMs elicit fulvestrant-like transcriptional programs in ER+ breast cancer cells.NPJ breast cancer · 2022Article
- Evolution of 3-(4-hydroxyphenyl)indoline-2-one as a scaffold for potent and selective anticancer activity.RSC medicinal chemistry · 2022Review
- Article
- Human Estrogen Receptor Alpha Antagonists, Part 3: 3-D Pharmacophore and 3-D QSAR Guided Brefeldin A Hit-to-Lead Optimization toward New Breast Cancer Suppressants.Molecules (Basel, Switzerland) · 2022Article
- Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer.Journal of medicinal chemistry · 2022Article
- Combined Estrogen Alpha and Beta Receptor Expression Has a Prognostic Significance for Colorectal Cancer Patients.Frontiers in medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complex tissue-specific and cell-specific signaling by the estrogen receptor (ER) frequently leads to the development of resistance to endocrine therapy for breast cancer. Pure ER antagonists, which completely lack tissue-specific agonist activity, hold promise for preventing and treating endocrine resistance, however an absence of structural information hinders the development of novel candidates. Here we synthesize a small panel of benzopyrans with variable side chains to identify pure antiestrogens in a uterotrophic assay. We identify OP-1074 as a pure antiestrogen and a selective ER degrader (PA-SERD) that is efficacious in shrinking tumors in a tamoxifen-resistant xenograft model. Biochemical and crystal structure analyses reveal a structure activity relationship implicating the importance of a stereospecific methyl on the pyrrolidine side chain of OP-1074, particularly on helix 12.
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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.