Titre :

Development of novel inhibitors targeting the d-box of the dna binding domain of androgen receptor

Auteur(s) :

Radaeva, Mariia [Auteur]

Ban, Fuqiang [Auteur]

Zhang, Fan [Auteur]

Leblanc, Eric [Auteur]
Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192
Lallous, Nada [Auteur]

Rennie, Paul S. [Auteur]

Gleave, Martin E. [Auteur]

Cherkasov, Artem [Auteur]

Titre de la revue :

International Journal of Molecular Sciences

Nom court de la revue :

Int. J. Mol. Sci.

Numéro :

22

Pagination :

2493

Date de publication :

2021-03-02

ISSN :

1422-0067

Mot(s)-clé(s) :

androgen receptor
prostate cancer
small-molecule inhibitors
computer-aided drug discovery
dimerization

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

The inhibition of the androgen receptor (AR) is an established strategy in prostate cancer (PCa) treatment until drug resistance develops either through mutations in the ligand-binding domain (LBD) portion of the receptor ...
Lire la suite >The inhibition of the androgen receptor (AR) is an established strategy in prostate cancer (PCa) treatment until drug resistance develops either through mutations in the ligand-binding domain (LBD) portion of the receptor or its deletion. We previously identified a druggable pocket on the DNA binding domain (DBD) dimerization surface of the AR and reported several potent inhibitors that effectively disrupted DBD-DBD interactions and consequently demonstrated certain antineoplastic activity. Here we describe further development of small molecule inhibitors of AR DBD dimerization and provide their broad biological characterization. The developed compounds demonstrate improved activity in the mammalian two-hybrid assay, enhanced inhibition of AR-V7 transcriptional activity, and improved microsomal stability. These findings position us for the development of AR inhibitors with entirely novel mechanisms of action that would bypass most forms of PCa treatment resistance, including the truncation of the LBD of the AR.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

INSERM
Université de Lille

Collections :

• Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192

Date de dépôt :

2022-06-15T14:00:05Z
2023-03-08T10:02:32Z