The androgen receptor (AR) pathway drives most metastatic, castration-resistant prostate cancers (mCRPC). Anti-androgen resistance mechanisms include AR gene amplification, C-terminal ligand-binding domain (LBD) mutations and expression of constitutively-active truncated AR splice variants lacking the LBD altogether (eg. AR-V7). Selective inhibition of the N-terminal domain (NTD) of the AR can prevent transcriptional activity even in the presence of LBD-driven resistance [1]. ESSA Pharma has developed EPI-7386, a potent and selective small molecule inhibitor that can bind to the N-terminal domain (NTD) of the androgen receptor (AR). EPI-7386 is currently in clinical trials for the treatment of patients with metastatic castration-resistant prostate cancer.

At the recent AACR-NCI-EORTC Virtual International Conference (7-10 October 2021), ESSA Pharma has presented some remarkable results showing preclinical characterization of the mechanism of action of EPI-7386 on the AR-NTD. ESSA Pharma collaborated with ZoBio to use our expertise in NMR for this characterization.  We used three different NMR approaches to unequivocally demonstrate for the first time binding of EPI-7836 to AR-NTD. We are proud to participate in this ground-breaking project.

Check out the virtual poster here!

 

[1] R. Le Moigne et al., Annals of Oncology., 2019, v.30, p.189-190