EPI-001 is a Selective Inhibitor of Androgen Receptor with Anti-tumor Activity

The androgen receptor (AR) is a type of nuclear receptor and a modular steroid hormone receptor transcription factor. Specifically, the androgen receptor is activated by binding any of the androgenic hormones then translocating into the nucleus. Besides, the main function of the androgen receptor is to regulate gene expression of DNA binding transcription factors. Besides, androgen regulatory genes are essential for the development and maintenance of male sexual phenotypes. Furthermore, the androgen receptor is the driver of prostate cancer (PCA) cell growth and disease progression. Normal and cancerous prostate tissues rely on androgen receptor activation to support cell proliferation and survival. Furthermore, androgen receptor has unique functional domains, including ligand-binding domain (LBD), DNA binding domain (DBD), and amino-terminal domain (NTD). EPI-001 is a selective Androgen Receptor (AR) inhibitor.

EPI-001 is a selective Androgen Receptor (AR) inhibitor with anti-tumor activity.

But, how does YUKA1 protect against cancer cells via KDM5A? Let’s discuss it in detail. First of all, EPI-001 is a selective  Androgen Receptor (AR) inhibitor. Nonetheless, EPI-001 can inhibit transactivation of the AR amino-terminal domain (NTD), with an IC₅₀ of 6 μM. Nonetheless, EPI-001 is also a selective modulator of PPARγ. EPI-001 exhibits anti-tumor activity in vitro and in vivo.

In the second place, EPI-001 inhibits PCa/CRPC cell growth in a dose-dependent manner with 5-100 μM. Nonetheless, EPI-001 inhibits the growth of AR-negative PC-3 and DU 145 cell lines as well as the T47D breast carcinoma cell line. Nonetheless, EPI-001 inhibits endogenous AR mRNA and protein expression in PCa and CRPC cell lines with 50 μM. EPI-001 inhibits transcriptional activity of both AR TAU1 and TAU5.

Last but not the least, EPI-00 reduced tumors from 100.3 mm³ to 73.03 mm³ within 2 weeks in vivo with 20 mg/kg of i.v. in every 5 d for 25 d. Nonetheless, EPI-00 blocks the androgen-axis and inhibits androgen-dependent tumor growth of 50 mg/kg. By the way, EPI-00 does not cause general toxicity indicated by no change in animal behavior or body weight.

All in all, EPI-001 is a selective Androgen Receptor (AR) inhibitor with anti-tumor activity.

References:

Andersen RJ, et, al. Cancer Cell. 2010 Jun 15; 17(6): 535-46.

Brand LJ, et, al. Oncotarget. 2015 Feb 28; 6(6): 3811-24.