ArticleACS pharmacology & translational science2019
Revealing Metabolic Liabilities of Ralaniten To Enhance Novel Androgen Receptor Targeted Therapies.
Article in ACS pharmacology & translational science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02606123 (A Phase 1/2 Open-Label Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral EPI-506 in Patients With Metastatic Castration-Resistant Prostate Cancer), which is not on this map. Cited by 17 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.
A Phase 1/2 Open-Label Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral EPI-506 in Patients With Metastatic Castration-Resistant Prostate Cancer
Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Drugging the intrinsically disordered transactivation domain of androgen receptor.Signal transduction and targeted therapy · 2026Article
- Emerging Therapeutic Approaches to Engage the Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer.Cancers · 2025Review
- Treatments Targeting the Androgen Receptor and Its Splice Variants in Breast Cancer.International journal of molecular sciences · 2024Review
- N-terminal domain of androgen receptor is a major therapeutic barrier and potential pharmacological target for treating castration resistant prostate cancer: a comprehensive review.Frontiers in pharmacology · 2024Review
- Hybrid Androgen Receptor Inhibitors Outperform Enzalutamide and EPI-001 in in vitro Models of Prostate Cancer Drug Resistance.ChemMedChem · 2023Article
- Article
- Drugging the Undruggable: Targeting the N-Terminal Domain of Nuclear Hormone Receptors.Advances in experimental medicine and biology · 2022Article
- AR Structural Variants and Prostate Cancer.Advances in experimental medicine and biology · 2022Article
- Review
- Pin1 inhibition improves the efficacy of ralaniten compounds that bind to the N-terminal domain of androgen receptor.Communications biology · 2021Article
- Isolation and characterization of castration-resistant prostate cancer LNCaP95 clones.Human cell · 2021Article
- Combination therapy with androgen receptor N-terminal domain antagonist EPI-7170 and enzalutamide yields synergistic activity in AR-V7-positive prostate cancer.Molecular oncology · 2020Article
- Article
- Mechanisms of Androgen Receptor Agonist- and Antagonist-Mediated Cellular Senescence in Prostate Cancer.Cancers · 2020Review
- Biologically active marine natural products and their molecular targets discovered using a chemical genetics approach.Natural product reports · 2020Review
- Discovery of drugs that directly target the intrinsically disordered region of the androgen receptor.Expert opinion on drug discovery · 2020Review
- A Clinical Evaluation of Enzalutamide in Metastatic Castration-Sensitive Prostate Cancer: Guiding Principles for Treatment Selection and Perspectives on Research.OncoTargets and therapy · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Inhibition of the androgen receptor (AR) is the mainstay treatment for advanced prostate cancer. Ralaniten (formally EPI-002) prevents AR transcriptional activity by binding to its N-terminal domain (NTD) which is essential for transcriptional activity. Ralaniten acetate (EPI-506) the triacetate pro-drug of ralaniten, remains the only AR-NTD inhibitor to have entered clinical trials (NCT02606123). While well tolerated, the trial was ultimately terminated due to poor pharmacokinetic properties and resulting pill burden. Here we discovered that ralaniten was glucuronidated which resulted in decreased potency. Long-term treatment of prostate cancer cells with ralaniten results in upregulation of UGT2B enzymes with concomitant loss of potency. This has proven to be a useful model with which to facilitate the development of more potent second-generation AR-NTD inhibitors. Glucuronidated metabolites of ralaniten were also detected in the serum of patients in Phase 1 clinical trials. Therefore, we tested an analogue of ralaniten (EPI-045) which was resistant to glucuronidation and demonstrated superiority to ralaniten in our resistant model. These data support that analogues of ralaniten designed to mitigate glucuronidation may optimize clinical responses to AR-NTD inhibitors.
Identifiers
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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.