Uses
EPI-001 is a selective peroxisome proliferator-activated receptor-gamma modulator that inhibits androgen receptor expression and activity in prostate cancer. It is a novel androgen receptor antagonists that has the potential for treating prostate cancer.
Definition
ChEBI: Bisphenol A (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) ether is the (3-chloro-2-hydroxypropyl) (2,3-dihydroxypropyl) diether of bisphenol A; a small molecule that inhibits transactivation of the AR amino-terminal domain (NTD). It has a role as an androgen antagonist. It is an organochlorine compound and a diether. It is functionally related to a bisphenol A and a glycerol.
Biological Activity
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].
References
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.
