title: 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.
abstract: The benzo[b]furan derivative MU314 inhibits in vitro bone resorption as potently as β-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 µg/kg) or E(2) (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 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.
authors: Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Japan.
authors: Ryo
authors: R
authors: Fukuyama
authors: Akio
authors: A
authors: Shimokawa
authors: Yasushi
authors: Y
authors: Kodama
authors: Mitsugu
authors: M
authors: Fujita
authors: Yoshitaka
authors: Y
authors: Ohishi
authors: Yuko
authors: Y
authors: Ando
authors: Masao
authors: M
authors: Koida
authors: Hiromichi
authors: H
authors: Nakamuta
references: Am J Obstet Gynecol. 1993 May;168(5):1473-80
references: 8498430
references: Bone. 1993 Jul-Aug;14(4):595-608
references: 8274302
references: JAMA. 1999 Aug 18;282(7):637-45
references: 10517716
references: Bone Miner. 1991 Dec;15(3):175-91
references: 1773131
references: Lancet. 2006 Jun 17;367(9527):2010-8
references: 16782492
references: Drug Saf. 2005;28(8):721-30
references: 16048357
references: Exp Cell Res. 2009 Apr 15;315(7):1287-301
references: 19331827
references: Proc Natl Acad Sci U S A. 1990 Sep;87(18):7260-4
references: 2169622
references: Bioorg Med Chem. 2009 Jun 1;17(11):3959-67
references: 19406645
references: Stroke. 2010 Oct;41(10 Suppl):S9-11
references: 20876515
references: Jpn J Pharmacol. 1999 Mar;79(3):379-86
references: 10230867
references: Bone. 1990;11(1):1-5
references: 2331425
references: Menopause. 2009 May-Jun;16(3):609-15
references: 19182697
references: J Steroid Biochem Mol Biol. 1992 Sep;43(1-3):173-7
references: 1525058
references: Nature. 1997 Nov 13;390(6656):175-9
references: 9367155
references: J Pharmacol Sci. 2008 Apr;106(4):530-5
references: 18431035
references: Cell. 2007 Sep 7;130(5):811-23
references: 17803905
references: Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3597-602
references: 9520411
references: Ann N Y Acad Sci. 2009 Oct;1179:70-85
references: 19906233
references: Bioorg Med Chem Lett. 2006 Nov 15;16(22):5849-54
references: 16945531
references: Calcif Tissue Res. 1967;1(1):24-32
references: 6060141
references: N Engl J Med. 1995 Jun 15;332(24):1589-93
references: 7753136
references: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14105-10
references: 9391160