Anti-osteoporosis Effect of 5-Bromo-2-(-chlorobenzoyl)-(Z)-3-(2-cyano-3-hydroxybut-2-enonyl)aminoben zo[b]furan: a Novel Selective Estrogen Receptor Modulator

作者：Fukuyama Ryo; Shimokawa Akio; Kodama Yasushi; Fujita Mitsugu; Ohishi Yoshitaka; Ando Yuko; Koida Masao; Nakamuta Hiromichi^*

来源：Journal of Pharmacological Sciences, 2011, 116(2): 214-220.

DOI：10.1254/jphs.11049FP

• selective estrogen receptor modulator
• osteoporosis
• osteoclast
• ovariectomy
• bone resorption

The benzo[b]furan derivative MU314 inhibits in vitro bone resorption as potently as,beta-estradiol (E(2)). Here, we examined the point of action on the anti-osteoporotic effects of MU314. MU314 (10 nM) suppressed lacunae formation by osteoclastic cells and ICI-182,780, a pure E(2) antagonist, inhibited this effect. Specifically, we ovariectomized (OVX) Wistar female rats and subcutaneously injected them with either MU314 (30 or 100 mu g/kg) or E(2) (100 mu g/kg) over an 8-week period. Bone mineral content (BMC) in the proximal end of the tibia was significantly decreased (14%) in OVX rats, and MU314 (100 mu g/kg) and E(2) significantly suppressed the decline in BMC. OVX rats exhibited decreased cancellous bone in the proximal end of the tibia and induced destruction of its trabecular structure. MU314 suppressed these changes. OVX also reduced the mechanical strength of the femoral neck, which was also recovered by MU314 and E(2). E(2) completely protected against OVX-induced uterine atrophy, but MU314 had no effect. These results strongly indicate that MU314 acts as a selective estrogen receptor modulator.

• 出版日期2011-6