Discovery of novel biphenyl derivatives as androgen receptor degraders for the treatment of enzalutamide-resistant prostate cancer.
Bioorg Chem
; 148: 107433, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38754311
ABSTRACT
Second-generation AR antagonists, such as enzalutamide, are the primary therapeutic agents for advanced prostate cancer. However, the development of both primary and secondary drug resistance leads to treatment failures and patient mortality. Bifunctional agents that simultaneously antagonize and degrade AR block the AR signaling pathway more completely and exhibit excellent antiproliferative activity against wild-type and drug-resistant prostate cancer cells. Here, we reported the discovery and optimization of a series of biphenyl derivatives as androgen receptor antagonists and degraders. These biphenyl derivatives exhibited potent antiproliferative activity against LNCaP and 22Rv1 cells. Our discoveries enrich the diversity of small molecule AR degraders and offer insights for the development of novel AR degraders for the treatment of enzalutamide-resistant prostate cancer.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Feniltioidantoína
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Neoplasias da Próstata
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Benzamidas
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Compostos de Bifenilo
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Receptores Androgênicos
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Resistencia a Medicamentos Antineoplásicos
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Proliferação de Células
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Antagonistas de Receptores de Andrógenos
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Antineoplásicos
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Nitrilas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article