ar-fl

IPI-9119 is an orally active, selective, and irreversible FASN inhibitor (IC50 = 0.3 nM).

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.

PROTAC AR Degrader-8 (Compound NP18) functions as a PROTAC degrader targeting the androgen receptor (AR) and effectively degrades AR-FL in both 22Rv1 and LNCaP cells with DC50 values of 0.018 μM and 0.14 μM, respectively. It also degrades AR-V7 in 22Rv1 cells with a DC50 of 0.026 μM. Additionally, PROTAC AR Degrader-8 inhibits the proliferation of 22Rv1 and LNCaP cancer cells, exhibiting IC50 values of 0.038 μM and 1.11 μM. It induces cell cycle arrest at the G2 M phase and triggers apoptosis in 22Rv1 cells (apoptosis). Demonstrating anticancer efficacy, PROTAC AR Degrader-8 shows activity in both mouse and zebrafish models. [Pink: ligand for target protein AR ligand-33; Black: linker; Blue: ligand for E3 ligase Cereblon]

EPI-7170 is a ralaniten analogue and a potent antagonist of the androgen receptor N-terminal structural domain, blocking the transcriptional activity of the full-length AR (FL-AR) and AR splice variants (AR-Vs). EPI-7170 exhibits antitumor activity against enzalutamide resistant debulking resistant prostate cancer (CRPC).

MTX-23, an AR-targeted Proteolysis Targeting Chimera (PROTAC), effectively degrades both AR-V7 and AR-FL, inhibiting the proliferation of CaP cells and inducing apoptosis [1].

BWA-522 is a small molecule, orally available protein-targeting chimera (PROTAC) that potentates the degradation of both full-length androgen receptor (AR-FL) and the AR-V7 splice variant. It specifically antagonizes the N-terminal domain (AR-NTD) of the androgen receptor (Androgen Receptor), prompting apoptosis in prostate cancer (PC) cells. In LNCaP xenograft models, BWA-522 demonstrated tumor growth inhibition (60 mg kg, po; TGI=76%). The compound effectively reduced levels of AR-V7 and AR-FL by 77.3% at 1 μM and 72.0% at 5 μM, respectively, in VCaP and LNCaP cell lines [1].

(R)-SKBG-1 is an inhibitor of the RNA-binding protein NONO, with an EC50 value of 1.5 μM in 22Rv1 cells. (R)-SKBG-1 reduces mRNA and protein expression of the androgen receptor (AR) and its splice variants (AR-FL and AR-V7), inhibits the proliferation of various cancer cells, and affects the transcriptome and proteome of cancer cells.

SC912 is an AR-V7 inhibitor with an IC50 of 0.36 μM. It directly binds to AR-FL and AR-V7 proteins, preventing their nuclear localization and chromatin binding. SC912 can exert anticancer effects by suppressing cell proliferation, inducing cell cycle arrest, and promoting apoptosis.