ArticleClinical cancer research : an official journal of the American Association for Cancer Research2026
Discovery of BMS-986365, a First-in-Class Dual Androgen Receptor Ligand-Directed Degrader and Antagonist, for the Treatment of Advanced Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06764485 (A Phase 3, Two-part, Randomized, Open-label, Adaptive Study Comparing BMS-986365 Versus Investigator's Choice of Therapy Comprising Either Docetaxel or Second Androgen Receptor Pathway Inhibitor), which is not on this map. Cited by 9 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 3, Two-part, Randomized, Open-label, Adaptive Study Comparing BMS-986365 Versus Investigator's Choice of Therapy Comprising Either Docetaxel or Second Androgen Receptor Pathway Inhibitor (ARPI), in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) - rechARge
Who cites it
9 citing papers in PubMed.
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- Induced proximity-based therapeutics for advanced prostate cancer.npj drug discovery · 2026Review
- Mepce Restrains Ferroptosis in Prostate Cancer Through 7SK-P-TEFb Pause Control.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dual PROTACs Versus Dual Inhibitors in Oncology: A Medicinal Chemistry and Linker Design Perspective.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Targeting the Androgen Receptor Pathway in Prostate Cancer: A PROTrACted Struggle.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- An Update on Clinically Advanced PROTAC Degraders and Their Synthesis.Molecules (Basel, Switzerland) · 2025Review
- Targeting androgen receptor signaling to enhance cancer immunotherapy.Trends in pharmacological sciences · 2025Review
- Emerging Therapeutic Approaches to Engage the Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer.Cancers · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors.
Funding
Abstract
purposeBMS-986365, a heterobifunctional androgen receptor (AR) ligand-directed degrader, was designed as a potent cereblon-dependent degrader and competitive antagonist of the AR to overcome resistance to AR pathway inhibition (ARPI) in metastatic prostate cancer. EXPERIMENTAL
designThe in vitro impact of BMS-986365-induced AR degradation on AR activity and prostate cancer cell proliferation was evaluated. Intrinsic agonistic and antagonist activities of BMS-986365 were assessed. The in vivo antitumor activity of BMS-986365 was compared with enzalutamide in multiple cell line- or patient-derived prostate cancer models.
resultsBMS-986365 is a potent, rapid, and selective degrader of AR wild-type (WT) and most of the clinically relevant mutants. Degradation of both WT and mutant AR is the key driver of BMS-986365 efficacy, with additional antagonism of residual AR activity enabled through occupancy of its ligand-binding domain. Compared with enzalutamide, BMS-986365 more efficiently inhibits AR target gene transcription and AR-dependent proliferation of prostate cancer cell lines. Whereas enzalutamide increased AR protein in metastatic castration-resistant prostate cancer (CRPC) models, BMS-986365 maintained low levels of AR protein despite increased AR transcript levels. In vivo, BMS-986365 demonstrated on-target activity, degrading AR, suppressing AR signaling, and inhibiting growth in validated cell line- and patient-derived xenograft models of castration-sensitive prostate cancer and advanced and/or therapy-resistant CRPC. Clinically, BMS-986365 reduced PSA in patients with metastatic CRPC after ARPI, including patients with WT AR.
conclusionsThe preclinical observations, coupled with clinical data, strongly support the potential for BMS-986365 to overcome ARPI-resistant disease regardless of AR mutational status. These findings establish BMS-986365 as a first-in-class dual AR degrader and competitive antagonist, likely to emerge as an important tool in the armamentarium to treat prostate cancer. See related commentary by Nyquist and Nelson, p. 13.
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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.