Arzoxifene (hydrochloride)

Arzoxifene (LY353381) 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. IC50 & Target: Estrogen receptor^[1] In Vitro: 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]. In Vivo: 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].