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.
Mol Cancer Ther
; 20(5): 763-774, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33649102
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antagonistas de Receptores de Andrógenos
/
Neoplasias de Próstata Resistentes à Castração
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Domínios Proteicos
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Mol Cancer Ther
Assunto da revista:
ANTINEOPLASICOS
Ano de publicação:
2021
Tipo de documento:
Article