Anti-osteoporosis Effect of 5-Bromo-2-(4-chlorobenzoyl)-(Z)-3-(2-cyano-3-hydroxybut-2-enonyl)aminobenzo[b]furan: a Novel Selective Estrogen Receptor Modulator

Journal of Pharmacological Sciences

Yuko Ando¹  Yoshitaka Ohishi¹  Akio Shimokawa²  Yasushi Kodama³  Hiromichi Nakamuta⁴  Mitsugu Fujita⁴  Ryo Fukuyama⁴  Masao Koida⁵ 

[1] School of Pharmaceutical Sciences, Mukogawa Women’s University, Japan;Department of Pharmacy, National Hospital Organization Kanmon Medical Center, Japan;Laboratory of Molecular and Cellular Pharmacology, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Hiroshima International University, Japan;Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Hiroshima International University, Japan;Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Japan

关键词: selective estrogen receptor modulator;    osteoporosis;    osteoclast;    ovariectomy;    bone resorption;   

DOI  :  10.1254/jphs.11049FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(25)Cited-By(1)The benzo[b]furan derivative MU314 inhibits in vitro bone resorption as potently as β-estradiol (E2). 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 E2 antagonist, inhibited this effect. Specifically, we ovariectomized (OVX) Wistar female rats and subcutaneously injected them with either MU314 (30 or 100 μg/kg) or E2 (100 μg/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 μg/kg) and E2 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 E2. E2 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.

【 授权许可】

Unknown