ArticleCommunications biology2018
Androgen receptor degradation by the proteolysis-targeting chimera ARCC-4 outperforms enzalutamide in cellular models of prostate cancer drug resistance.
Article in Communications biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers, 1 of them a synthesis that pooled it.
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Who cites it
183 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations.Prostate cancer and prostatic diseases · 2020Pooled it
- Context matters in PROTAC design: navigating the trade-off between degradation and developability.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- A TERRA-NONO axis drives fibroblast reprogramming in cancer.Science advances · 2026Article
- Beyond androgen deprivation therapy: Next-generation hormonal therapies and emerging combination approaches in advanced prostate cancer.Urologic oncology · 2026Review
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Evolving Treatments and Resistance Mechanisms in Prostate Cancer Therapeutics.ACS pharmacology & translational science · 2026Review
- Phase I multi-center clinical and biomarker study of the dual-action androgen receptor inhibitor ONCT-534.Investigational new drugs · 2026Article
- Androgen Receptor Point Mutations: A Mechanism of Therapeutic Resistance and a Framework for Rational Drug Design.Cancers · 2026Review
- Combinatorial use of VHL and KEAP1 PROTACs reveals unexpected synergy and hook effect relief.Genes & development · 2026Article
- Inhibition of nuclear import suppresses androgen receptor action and overcomes resistance in prostate cancer.BMC cancer · 2026Article
- Emerging therapies to overcome antiandrogen resistance and beyond in lethal prostate cancer.Journal of the National Cancer Center · 2026Review
- Conformational Dynamics in the Cell Membrane Interactions of Bispecific Targeted Degrader Therapeutics.Journal of medicinal chemistry · 2025Article
- Ion channel inhibition by targeted recruitment of NEDD4-2 with divalent nanobodies.Nature communications · 2025Article
- A comprehensive kinetic model for ternary complex catalysis.Scientific reports · 2025Article
- PROTAC repurposing uncovers a noncanonical binding surface that mediates chemical degradation of nuclear receptors.Nature communications · 2025Article
- Discovery of LD-110 as an Effective LSD1 PROTAC Degrader for the Treatment of Esophagus Squamous Cancer.Journal of medicinal chemistry · 2025Article
- Discovery of dCDK9-202 as a Highly Potent and Selective PROTAC CDK9 Degrader with StrongJournal of medicinal chemistry · 2025Article
- Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge.Journal of molecular biology · 2025Review
- Single cell transcriptomics reveals enrichment of aggregation-prone alpha-synuclein isoforms across synucleinopathies.bioRxiv : the preprint server for biology · 2025Article
123 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The androgen receptor is a major driver of prostate cancer and inhibition of its transcriptional activity using competitive antagonists, such as enzalutamide remains a frontline therapy for prostate cancer management. However, the majority of patients eventually develop drug resistance. We propose that targeting the androgen receptor for degradation via Proteolysis Targeting Chimeras (PROTACs) will be a better therapeutic strategy for targeting androgen receptor signaling in prostate cancer cells. Here we perform a head-to-head comparison between a currently approved androgen receptor antagonist enzalutamide, and its PROTAC derivative, ARCC-4, across different cellular models of prostate cancer drug resistance. ARCC-4 is a low-nanomolar androgen receptor degrader able to degrade about 95% of cellular androgen receptors. ARCC-4 inhibits prostate tumor cell proliferation, degrades clinically relevant androgen receptor point mutants and unlike enzalutamide, retains antiproliferative effect in a high androgen environment. Thus, ARCC-4 exemplifies how protein degradation can address the drug resistance hurdles of enzalutamide.
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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.