Arzoxifene hydrochloride (LY 353381 HCl)

Arzoxifene hydrocloride is a selective estrogen receptor modulator that is a potent estrogen antagonist in mammary and uterine tissue while acting as an estrogen agonist to maintain bone density and lower serum cholesterol.

Arzoxifene inhibits cell growth as effectively as the antiestrogen tamoxifen. Northern analysis reveals that arzoxifene exerts a statistically significant inhibition of pS2 and progesterone receptor B mRNA expression. Significant agonistic effect is observed on the antitrypsin mRNA expression. In contrast to estradiol and tamoxifen, arzoxifene does not upregulate cathepsin D mRNA and protein expression[1].

Arzoxifene prevents the ovariectomy-induced increase in body weight and serum cholesterol levels of treated rats and lowers them to below sham levels in a dose dependent manner, with maximum efficacy similar to estrogen or raloxifene. Arzoxifene (LY353381.HCl) prevents loss of bone due to ovariectomy with an ED50 of about 0.01 mg/kg with maximal efficacy observed at 0.1-1 mg/kg/day. Arzoxifene (LY353381.HCl) antagonizes the estrogen-induced elevation in uterine weight down to vehicle-dosed control levels with ED50 of 0.03 mg/kg/day[2].

[1]. Suh N, et al. Arzoxifene, a new selective estrogen receptor modulator for chemoprevention of experimental breast cancer. Cancer Res. 2001 Dec 1;61(23):8412-5.