ArticleThe Journal of biological chemistry2014
Selectively targeting the DNA-binding domain of the androgen receptor as a prospective therapy for prostate cancer.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers.
What it found
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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
71 citing papers in PubMed.
- Beyond androgen deprivation therapy: Next-generation hormonal therapies and emerging combination approaches in advanced prostate cancer.Urologic oncology · 2026Review
- Limitations of Molecular Docking in Predicting the Selectivity of Selective Androgen Receptor Modulators (SARMs): A Comparative Study of YK11 and Ostarine Across Five Nuclear Receptors.International journal of molecular sciences · 2026Article
- C620Y Mutation-Induced Destabilization of the Androgen Receptor Disrupts DNA Recognition Specificity in Prostate Cancer: Insights from Extensive Parametric Normal Mode Simulations.Cell biochemistry and biophysics · 2026Article
- An Optimized RNF126-Targeting Covalent Handle for Molecular Glue Degraders.bioRxiv : the preprint server for biology · 2026Article
- Benzotriazole in Cancer: A Systematic Review on Preclinical Evidence and Structure-Activity Relationship.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- DCAF16-Based Covalent Degradative Handles for the Modular Design of Degraders.ACS central science · 2025Article
- Androgen receptor inhibitors in treating prostate cancer.Asian journal of andrology · 2025Review
- Looking beyond the ER, PR, and HER2: what's new in the ARsenal for combating breast cancer?Reproductive biology and endocrinology : RB&E · 2025Review
- New opportunities to overcome T cell dysfunction: the role of transcription factors and how to target them.Trends in biochemical sciences · 2024Review
- Treatments Targeting the Androgen Receptor and Its Splice Variants in Breast Cancer.International journal of molecular sciences · 2024Review
- Rational Chemical Design of Molecular Glue Degraders.ACS central science · 2023Article
- The androgen receptor-targeted proteolysis targeting chimera and other alternative therapeutic choices in overcoming the resistance to androgen deprivation treatment in prostate cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Dynamic phase separation of the androgen receptor and its coactivators key to regulate gene expression.Nucleic acids research · 2023Article
- Constitutively Active Androgen Receptor in Hepatocellular Carcinoma.International journal of molecular sciences · 2022Review
- Structure-Based Study to Overcome Cross-Reactivity of Novel Androgen Receptor Inhibitors.Cells · 2022Article
- Second generation androgen receptor antagonists and challenges in prostate cancer treatment.Cell death & disease · 2022Review
- (+)-JJ-74-138 is a Novel Noncompetitive Androgen Receptor Antagonist.Molecular cancer therapeutics · 2022Article
- Regulation of AR mRNA translation in response to acute AR pathway inhibition.Nucleic acids research · 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
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
- Erratum issuedHessein, Mohamed [Corrected to Hassona, Mohamed D]
Authors and funding
13 authors.
Funding
Abstract
The androgen receptor (AR) is a transcription factor that has a pivotal role in the occurrence and progression of prostate cancer. The AR is activated by androgens that bind to its ligand-binding domain (LBD), causing the transcription factor to enter the nucleus and interact with genes via its conserved DNA-binding domain (DBD). Treatment for prostate cancer involves reducing androgen production or using anti-androgen drugs to block the interaction of hormones with the AR-LBD. Eventually the disease changes into a castration-resistant form of PCa where LBD mutations render anti-androgens ineffective or where constitutively active AR splice variants, lacking the LBD, become overexpressed. Recently, we identified a surfaced exposed pocket on the AR-DBD as an alternative drug-target site for AR inhibition. Here, we demonstrate that small molecules designed to selectively bind the pocket effectively block transcriptional activity of full-length and splice variant AR forms at low to sub-micromolar concentrations. The inhibition is lost when residues involved in drug interactions are mutated. Furthermore, the compounds did not impede nuclear localization of the AR and blocked interactions with chromatin, indicating the interference of DNA binding with the nuclear form of the transcription factor. Finally, we demonstrate the inhibition of gene expression and tumor volume in mouse xenografts. Our results indicate that the AR-DBD has a surface site that can be targeted to inhibit all forms of the AR, including enzalutamide-resistant and constitutively active splice variants and thus may serve as a potential avenue for the treatment of recurrent and metastatic prostate cancer.
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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.