A novel androgen receptor antagonist JJ-450 inhibits enzalutamide-resistant mutant AR^F876L nuclear import and function.

ABSTRACT:

Background

Castration-resistant prostate cancer can develop resistance to enzalutamide because of androgen receptor (AR) point mutations, AR overexpression, constitutively active AR splice variants, and/or elevated intratumoral androgen synthesis. The point mutation AR^F876L was reported to be stimulated, instead of inhibited, by enzalutamide, thus contributing to enzalutamide resistance. We have recently developed JJ-450 as a novel AR antagonist with the potential to treat enzalutamide-resistant castration-resistant prostate cancer (CRPC).

Methods

We employed several assays to determine the impact of JJ-450 and enzalutamide on prostate cancer cell lines expressing green fluorescent protein (GFP)-AR^F876L . These assays include a prostate-specific antigen

SUBMITTER: Wu Z 

PROVIDER: S-EPMC7421602 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature