ar-lbd

UT-155 is a selective and potent antagonist of the androgen receptor (AR) with a binding affinity (Ki) of 267 nM for the AR ligand-binding domain (AR-LBD).

Luxdegalutamide (ARV-766) is a PROTAC and a protein degrader targeting the androgen receptor, capable of effectively degrading wild-type and drug-resistant mutants including L702H, H875Y, and T878A. With oral bioactivity and cell permeability, this compound is used in castration-resistant prostate cancer research and exhibits significant antitumor activity.

SC428 acts as an inhibitor of the androgen receptor (AR), specifically targeting the N-terminal domain of AR. This compound effectively diminishes the transactivation of various AR forms, including AR-V7, ARv567es, full-length AR (AR-FL), and its LBD mutants. Additionally, SC428 significantly inhibits AR-FL nuclear translocation, chromatin binding, and AR-regulated gene transcription under androgen stimulation. In vitro, SC428 suppresses the proliferation of tumor cells. In vivo, it inhibits tumor growth in mice transplanted with 22Rv1 cells by inducing apoptosis.

(+)-JJ-450 is a non-competitive antagonist that targets the androgen receptor (AR), inhibiting nuclear localization and transcriptional activity of AR under androgen-deprived conditions. In LN95 cells, (+)-JJ-450 is less effective than (-)-JJ-450 at inhibiting prostate-specific antigen (PSA) expression, likely due to its targeting of the AR ligand-binding domain (LBD). The compound works by promoting degradation of unbound AR within the nucleus and reducing AR binding to androgen response elements (AREs), thus inhibiting the transcriptional activity of AR and its splicing variants like ARv7. Additionally, (+)-JJ-450 is applicable for research in castration-resistant prostate cancer (CRPC) that is resistant to Enzalutamide (MDV3100).

JJ-450 is a non-competitive antagonist that targets androgen receptors (AR), capable of inhibiting the transcriptional activity of both wild-type AR and mutant ARF876L. It demonstrates an IC50 of approximately 1-10 μM for suppressing AR transcriptional activity in PC3 cells and selectively binds to AR without competing for the ligand binding domain (LBD) with androgens. JJ-450 functions by inhibiting the nuclear translocation of AR and promoting the degradation of unbound ligand AR within the nucleus, thereby suppressing the transcriptional activity of AR and its splice variants, such as ARF876L. This compound can be utilized in studies of castration-resistant prostate cancer (CRPC) that are resistant to Enzalutamide (MDV3100).

(-)-JJ-450 is a non-competitive antagonist targeting the androgen receptor (AR). It is more effective than (+)-JJ-450 in inhibiting androgen-induced AR activity, while (+)-JJ-450 inhibits AR via a mechanism distinct from Enzalutamide (MDV3100), possibly targeting the ligand-binding domain (LBD) of AR. (-)-JJ-450 inhibits transcriptional activity of both wild-type AR and the mutant ARF876L by suppressing AR nuclear translocation and promoting intranuclear degradation of unbound AR. This compound can be utilized in research focusing on castration-resistant prostate cancer (CRPC) that is resistant to Enzalutamide.