Background:

EPI-001 is a small-molecule inhibitor of androgen receptor N-terminal domain. EPI-001 could target the amino terminal domain of the AR and inhibit the protein-protein interactions which are necessary for AR transcriptional activity. The androgen receptor (AR) is involved in mediating the actions of male sex steroids. Amplification and over-expression of androgen receptor gene may result in hormone-refractory prostate cancer [1].

In vitro: EPI-001 inhibited the ligand-dependent ARGal4 transcriptional activity in LNCaP cells and the ligand-independent ARGal4 transcriptional activity in the CRPC C4-2 cell line. In a panel of cell lines, EPI-001 treatment decreased the mRNA expression level of AR protein after 8 and 16 h treatment, such as androgen sensitive PCa, CRPC, LNCap, C4-2, and LAPC4 cell line. EPI-001 dose-dependently inhibited the PCa/CRPC cell growth [2].

In vivo: Intravenous injection of EPI-001 significantly reduced the weight of benign prostates and blocked the growth of prostate cancer xenograft from noncastrated mature mice. EPI-001 caused tumor regression of CRPC. In male mice bearing LNCaP xenografts, after treated with EPI- 001 by i.v. injection for 2 weeks, the tumor size was less than half of the control group [3].

参考文献:
Andersen R J, Mawji N R, Wang J, et al.  Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor[J]. Cancer cell, 2010, 17(6): 535-546.
Brand L J, Olson M E, Ravindranathan P, et al.  EPI-001 is a selective peroxisome proliferator-activated receptor-gamma modulator with inhibitory effects on androgen receptor expression and activity in prostate cancer[J]. Oncotarget, 2015, 6(6): 3811.
Sadar M D.  Small molecule inhibitors targeting the “achilles' heel” of androgen receptor activity[J]. Cancer research, 2011, 71(4): 1208-1213.