ArticleACS chemical biology2013
Selectively targeting prostate cancer with antiandrogen equipped histone deacetylase inhibitors.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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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
29 citing papers in PubMed, 63 citations in OpenAlex.
- Review
- Repositioning Antihistamine for Cancer Therapy: Clemizole as a Template for the Design of Liver Tissue-Targeting Epigenetic-Modifying Agents.Journal of medicinal chemistry · 2026Article
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- Article
- Discovery of Primaquine-Indole Carboxamides with Cancer-Cell-Selective Antiproliferative Activity.Molecules (Basel, Switzerland) · 2025Article
- Small-molecule disruption of androgen receptor-dependent chromatin clusters.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- GαCancers · 2024Article
- Article
- Epigenetics in prostate cancer: clinical implications.Translational andrology and urology · 2021Review
- Shifting the paradigm in treating multi-factorial diseases: polypharmacological co-inhibitors of HDAC6.RSC medicinal chemistry · 2021Review
- Article
- Article
- Systematic Investigation of the Permeability of Androgen Receptor PROTACs.ACS medicinal chemistry letters · 2020Article
- Chemical genomics reveals histone deacetylases are required for core regulatory transcription.Nature communications · 2019Article
- Androgen Receptor-Directed Molecular Conjugates for Targeting Prostate Cancer.Frontiers in chemistry · 2019Review
- Design, synthesis, and evaluation of the antiproliferative activity of hydantoin-derived antiandrogen-genistein conjugates.Bioorganic & medicinal chemistry · 2018Article
- Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase.Bioorganic & medicinal chemistry · 2017Article
- Hybrid Enzalutamide Derivatives with Histone Deacetylase Inhibitor Activity Decrease Heat Shock Protein 90 and Androgen Receptor Levels and Inhibit Viability in Enzalutamide-Resistant C4-2 Prostate Cancer Cells.Molecular pharmacology · 2016Article
- CUDC-101, a Novel Inhibitor of Full-Length Androgen Receptor (flAR) and Androgen Receptor Variant 7 (AR-V7) Activity: Mechanism of Action and In Vivo Efficacy.Hormones & cancer · 2016Article
- Epigenetic modulators as therapeutic targets in prostate cancer.Clinical epigenetics · 2016Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Diverse cellular processes relevant to cancer progression are regulated by the acetylation status of proteins. Among such processes is chromatin remodeling via histone proteins, controlled by opposing histone deacetylase (HDAC) and histone acetyltransferase (HAT) enzymes. Histone deacetylase inhibitors (HDACi) show great promise in preclinical cancer models, but clinical trials treating solid tumors have failed to improve patient survival. This is due in part to an inability of HDACi to effectively accumulate in cancerous cells. To address this problem we designed HDACi with secondary pharmacophores to facilitate selective accumulation in malignant cells. We present the first example of HDACi compounds targeted to prostate tumors by equipping them with the additional ability to bind the androgen receptor (AR) with nonsteroidal antiandrogen moieties. Leads among these new dual-acting molecules bind to the AR and halt AR transcriptional activity at lower concentrations than clinical antiandrogens. They inhibit key isoforms of HDAC with low nanomolar potency. Fluorescent microscopy reveals varying degrees of AR nuclear localization in response to these compounds that correlates with their HDAC activity. These biological properties translate into potent anticancer activity against hormone-dependent (AR+) LNCaP and to a lesser extent against hormone-independent (AR-) DU145 prostate cancer, while having greatly reduced toxicity in noncancerous cells. This illustrates that engaging multiple biological targets with a single chemical probe can achieve both potent and cell-type-selective responses.
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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.