Androgen Receptor

The androgen receptor (AR) plays an essential role in controlling the effects of androgen hormones and cell growth in certain cancers including prostate and breast cancer.

The AR is composed of three domains:

Ligand-binding domain – binds to androgen hormones

DNA-binding domain – binds to DNA in cells

N-terminal domain – controls the ability of the AR to regulate gene transcription

The N-terminal domain controls the transcriptional activity of the AR, a critical function necessary for AR-driven cancer cell growth.

Cancer cell adaptations (such as mutations) maintain AR-driven tumor growth despite low circulating levels of androgen and despite the potential presence of androgen inhibitors. Furthermore, some truncated AR splice variants that lack a ligand-binding domain retain their activity independent of androgen and represent a resistance mechanism to existing hormone therapies.

By directly inhibiting the AR N-terminal domain, EPI compounds have the potential to overcome these biological adaptations.