Arzoxifene hydrochloride (C09-1102-162)

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 .In VitroArzoxifene 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoArzoxifene 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 ED 50 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 ED 50 of 0.03 mg/kg/day. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal administrationRats Antiestrogen activity is evaluated in 21-day old Sprague Dawley rats.17α-Ethynyl estradiol at 0.1 mg/kg/day is used as the estrogenic stimulus to increase uterine weight in these rats. Arzoxifene HCl (LY353381.HCl)LY353381.HCl (0.001-10 mg/kg) or raloxifene (1 mg/kg) are administered by oral gavage in a volume of 0.2 mL, 15 min prior to the EE2 gavage. Dosing with test compounds is continued for 3 consecutive days. Animals are fasted over night, following the final dose . aladdin has not independently confirmed the accuracy of these methods. They are for reference only.Form:SolidIC50& Target:Estrogen receptor. Specification: 0.98 Molecular Formula: C28H30ClNO4S Molecular Weight: 512.06 PubChem CID: 179338 Isomeric SMILES: COC1=CC=C(C=C1)C2=C(C3=C(S2)C=C(C=C3)O)OC4=CC=C(C=C4)OCCN5CCCCC5.Cl