Discovery of JNJ-63576253, a Next-Generation Androgen Receptor Antagonist Active Against Wild-Type and Clinically Relevant Ligand Binding Domain Mutations in Metastatic Castration-Resistant Prostate Cancer.
Journal
Molecular cancer therapeutics
ISSN: 1538-8514
Titre abrégé: Mol Cancer Ther
Pays: United States
ID NLM: 101132535
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
18
06
2020
revised:
22
10
2020
accepted:
25
02
2021
pubmed:
3
3
2021
medline:
29
12
2021
entrez:
2
3
2021
Statut:
ppublish
Résumé
Numerous mechanisms of resistance arise in response to treatment with second-generation androgen receptor (AR) pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC). Among these, point mutations in the ligand binding domain can transform antagonists into agonists, driving the disease through activation of AR signaling. To address this unmet need, we report the discovery of JNJ-63576253, a next-generation AR pathway inhibitor that potently abrogates AR signaling in models of human prostate adenocarcinoma. JNJ-63576253 is advancing as a clinical candidate with potential effectiveness in the subset of patients who do not respond to or are progressing while on second-generation AR-targeted therapeutics.
Identifiants
pubmed: 33649102
pii: 1535-7163.MCT-20-0510
doi: 10.1158/1535-7163.MCT-20-0510
doi:
Substances chimiques
Androgen Receptor Antagonists
0
Ligands
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
763-774Informations de copyright
©2021 American Association for Cancer Research.
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