Arzoxifene hydrochloride

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.

Signaling Pathways >> Others >> Estrogen Receptor/ERR

Research Areas >> Cancer

Estrogen receptor[1]

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].

For growth experiments, MCF-7 and MDA-MB-231 cells are treated with Arzoxifene HCl (LY353381.HCl) (0.1, 1, 10, 100, 1000 nM). Medium is renewed at days 3 and 5. At day 6, four wells are used for each cell-number determination by counting in a hemocytometer[1].

Rats[2] 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[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.

Elacestrant dihydrochloride | AZD9496 | Kaempferol | XCT 790 | Estrone | GDC-0810 | (20S)-Protopanaxatriol | 27-Hydroxycholesterol | Diethylstilbestrol | PHTPP | 2,3-bis(4-hydroxyphenyl)propionitrile | 4',7-Isoflavandiol | cholesterol | Chrysin | Endoxifen (Z-isomer hydrochloride)