ArticleJournal of medicinal chemistry2021
Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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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
47 citing papers in PubMed, 135 citations in OpenAlex.
- Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Mechanisms and Design Principles of Proteolysis-Targeting Chimeras and Their Emerging Applications.ACS pharmacology & translational science · 2026Review
- Androgen Receptor Point Mutations: A Mechanism of Therapeutic Resistance and a Framework for Rational Drug Design.Cancers · 2026Review
- Lessons learned in linking PROTACs from discovery to the clinic.Nature reviews. Chemistry · 2026Review
- Discovery of dCDK9-202 as a Highly Potent and Selective PROTAC CDK9 Degrader with StrongJournal of medicinal chemistry · 2025Article
- Discovery of LD-110 as an Effective LSD1 PROTAC Degrader for the Treatment of Esophagus Squamous Cancer.Journal of medicinal chemistry · 2025Article
- PROTACs therapeutically target the polyglutamine androgen receptor in spinal and bulbar muscular atrophy models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Targeting the mutant androgen receptor with PROTACs in spinal and bulbar muscular atrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Review
- MD-4251: A First-in-Class Oral MDM2 Degrader Inducing Complete Tumor Regression with Single-Dose Administration.Journal of medicinal chemistry · 2025Article
- Targeting the Undruggable: Recent Progress in PROTAC-Induced Transcription Factor Degradation.Cancers · 2025Review
- Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC).Journal of medicinal chemistry · 2025Article
- PROTAC technology for prostate cancer treatment.Acta materia medica · 2025Article
- Androgen Signaling in Prostate Cancer: When a Friend Turns Foe.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Discovery of ERD-1233 as a Potent and Orally Efficacious Estrogen Receptor PROTAC Degrader for the Treatment of ER+ Human Breast Cancer.Journal of medicinal chemistry · 2024Article
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- Discovery of ZLC491 as a Potent, Selective, and Orally Bioavailable CDK12/13 PROTAC Degrader.Journal of medicinal chemistry · 2024Article
- Tissue distribution and retention drives efficacy of rapidly clearing VHL-based PROTACs.Communications medicine · 2024Article
- Discovery of LLC0424 as a Potent and SelectiveJournal of medicinal chemistry · 2024Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Proteolysis targeting chimera (PROTAC) small-molecule degraders have emerged as a promising new type of therapeutic agents, but the design of PROTAC degraders with excellent oral pharmacokinetics is a major challenge. In this study, we present our strategies toward the discovery of highly potent PROTAC degraders of androgen receptor (AR) with excellent oral pharmacokinetics. Employing thalidomide to recruit cereblon/cullin 4A E3 ligase and through the rigidification of the linker, we discovered highly potent AR degraders with good oral pharmacokinetic properties in mice with ARD-2128 being the best compound. ARD-2128 achieves 67% oral bioavailability in mice, effectively reduces AR protein and suppresses AR-regulated genes in tumor tissues with oral administration, leading to the effective inhibition of tumor growth in mice without signs of toxicity. This study supports the development of an orally active PROTAC AR degrader for the treatment of prostate cancer and provides insights and guidance into the design of orally active PROTAC degraders.
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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.