ArticleACS chemical biology2014
Ligand-independent and tissue-selective androgen receptor inhibition by pyrvinium.
Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 57 citations in OpenAlex.
- Emerging Therapeutic Approaches to Engage the Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer.Cancers · 2025Review
- Androgen receptor inhibitors in treating prostate cancer.Asian journal of andrology · 2025Review
- Beyond the Horizon: Rethinking Prostate Cancer Treatment Through Innovation and Alternative Strategies.Cancers · 2024Article
- Androgen receptor and estrogen receptor variants in prostate and breast cancers.The Journal of steroid biochemistry and molecular biology · 2024Review
- Toxic Effects of Penetrating Cations.Membranes · 2023Review
- Metabolic modulation of mitochondrial mass during CD4Cell chemical biology · 2023Article
- A drug repurposing method based on inhibition effect on gene regulatory network.Computational and structural biotechnology journal · 2023Article
- Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug.Biomedicines · 2022Review
- Constitutively Active Androgen Receptor in Hepatocellular Carcinoma.International journal of molecular sciences · 2022Review
- Chronologically modified androgen receptor in recurrent castration-resistant prostate cancer and its therapeutic targeting.Science translational medicine · 2022Article
- AR Structural Variants and Prostate Cancer.Advances in experimental medicine and biology · 2022Article
- Discovery of novel antagonists targeting the DNA binding domain of androgen receptor by integrated docking-based virtual screening and bioassays.Acta pharmacologica Sinica · 2022Article
- A Novel Dialkylamino-Functionalized Chalcone, DML6, Inhibits Cervical Cancer Cell Proliferation, In Vitro, via Induction of Oxidative Stress, Intrinsic Apoptosis and Mitotic Catastrophe.Molecules (Basel, Switzerland) · 2021Article
- Eighty Years of Targeting Androgen Receptor Activity in Prostate Cancer: The Fight Goes on.Cancers · 2021Review
- The Androgen Receptor in Prostate Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy.Biomedicines · 2020Review
- Targeting the CK1α/CBX4 axis for metastasis in osteosarcoma.Nature communications · 2020Article
- Pyrvinium Pamoate Use in a B cell Acute Lymphoblastic Leukemia Model of the Bone Tumor Microenvironment.Pharmaceutical research · 2020Article
- Molecules targeting the androgen receptor (AR) signaling axis beyond the AR-Ligand binding domain.Medicinal research reviews · 2019Review
- Mechanistic Investigation of the Androgen Receptor DNA-Binding Domain Inhibitor Pyrvinium.ACS omega · 2019Article
- Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A pre-clinical assessment.Journal of cellular physiology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Pyrvinium pamoate (PP) is a potent noncompetitive inhibitor of the androgen receptor (AR). Using a novel method of target identification, we demonstrate that AR is a direct target of PP in prostate cancer cells. We demonstrate that PP inhibits AR activity via the highly conserved DNA binding domain (DBD), the only AR inhibitor that functions via this domain. Furthermore, computational modeling predicts that pyrvinium binds at the interface of the DBD dimer and the minor groove of the AR response element. Because PP acts through the DBD, PP is able to inhibit the constitutive activity of AR splice variants, which are thought to contribute to the growth of castration resistant prostate cancer (CRPC). PP also inhibits androgen-independent AR activation by HER2 kinase. The antiandrogen activity of pyrvinium manifests in the ability to inhibit the in vivo growth of CRPC xenografts that express AR splice variants. Interestingly, PP was most potent in cells with endogenous AR expression derived from prostate or bone. PP was able to inhibit several other hormone nuclear receptors (NRs) but not structurally unrelated transcription factors. PP inhibition of other NRs was similarly cell-type selective. Using dual-energy X-ray absorptiometry, we demonstrate that the cell-type specificity of PP manifests in tissue-selective inhibition of AR activity in mice, as PP decreases prostate weight and bone mineral density but does not affect lean body mass. Our results suggest that the noncompetitive AR inhibitor pyrvinium has significant potential to treat CRPC, including cancers driven by ligand-independent AR signaling.
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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.