ArticleEndocrinology2020
Bis-Indole-Derived Nuclear Receptor 4A1 (NR4A1, Nur77) Ligands as Inhibitors of Endometriosis.
Article in Endocrinology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The role of fibrosis in endometriosis: a systematic review.Human reproduction update · 2024Pooled it
- Article
- The Role of Dietary Supplements in the Treatment of Endometriosis: A Critical Review.Nutrients · 2026Review
- A Commentary on Dual Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 Ligands.Journal of cellular immunology · 2026Article
- Dual Targeting of Orphan Nuclear Receptors NR4A1 and NR4A2 for Nonhormonal Endometriosis Therapy.Endocrinology · 2025Article
- Review
- Perfluorooctane Sulfonate (PFOS) and Related Compounds Induce Nuclear Receptor 4A1 (NR4A1)-Dependent Carcinogenesis.Chemical research in toxicology · 2025Article
- Article
- N-Myc and STAT Interactor is an Endometriosis Suppressor.International journal of molecular sciences · 2024Article
- Comparative safety, pharmacokinetics, and off-target assessment of 1,1-bis(3'-indolyl)-1-(Toxicology research · 2024Article
- Unveiling the fibrotic puzzle of endometriosis: An overlooked concern calling for prompt action.F1000Research · 2024Review
- Flavonoids Quercetin and Kaempferol Are NR4A1 Antagonists and Suppress Endometriosis in Female Mice.Endocrinology · 2023Article
- hUMSCs Transplantation Regulates AMPK/NR4A1 Signaling Axis to Inhibit Ovarian Fibrosis in POI Rats.Stem cell reviews and reports · 2023Article
- Piperlongumine is a ligand for the orphan nuclear receptor 4A1 (NR4A1).Frontiers in pharmacology · 2023Article
- Oleuropein suppresses endometriosis progression and improves the fertility of mice with endometriosis.Journal of biomedical science · 2022Article
- Orphan nuclear receptor 4A1 (NR4A1) and novel ligands.Essays in biochemistry · 2021Article
- The Paradoxical Roles of Orphan Nuclear Receptor 4A (NR4A) in Cancer.Molecular cancer research : MCR · 2021Review
- Bladder Exposure toFrontiers in cellular and infection microbiology · 2021Article
- Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription.Cells · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Endometriosis is an inflammatory disease that primarily affects women during their reproductive years, and since current hormonal therapies are of concern, new hormone-independent treatment regimens are needed. The orphan nuclear receptor 4A1 (NR4A1, Nur77) is expressed in patient-derived (stromal) endometriotic cells and also epithelial cell lines, and we observed that knockdown of NR4A1 in patient-derived ectopic endometrium-isolated ovarian endometrioma (ESECT)-7 and ESECT-40 cells decreased cell proliferation and induced apoptosis. Moreover, the treatment of these cells with bis-indole derived NR4A1 ligands 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) and its buttressed 3-chloro-5-methoxy analog (DIM-C-pPhOH-3-Cl-5-OCH3) inhibited cell growth and induced apoptosis and related genes. The compounds exhibit NR4A1 antagonist activities in both functional and transactivation assays whereas these effects were not observed in normal endometrial cells. We also observed that NR4A1 knockdown and treatment with NR4A1 antagonists decreased fibrosis, α-smooth muscle actin, and related pro-fibrotic genes in ESECT-7 and ESECT-40 cells, and similar results were observed in epithelial-derived endometriotic cell lines. Moreover, in an endometriosis mouse model with auto-transplantation and also in severe combined immune deficiency mice transplanted with human endometriotic cells treatment with 25 mg/kg/day DIM-C-pPhOH-3-Cl-5-OCH3 significantly inhibited growth and expansion of endometriotic lesions. Thus, bis-indole-derived NR4A1 ligands represent a novel class of drugs as nonhormonal therapy for endometriosis.
Indexed as
Identifiers
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.