title: A novel carborane analog, BE360, with a carbon-containing polyhedral boron-cluster is a new selective estrogen receptor modulator for bone.
abstract: Carboranes are a class of carbon-containing polyhedral boron-cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors. Estrogen deficiency results in marked bone loss due to increased osteoclastic bone resorption in females, but estrogen replacement therapy is not generally used for postmenopausal osteoporosis due to the risk of uterine cancer. We synthesized a novel carborane compound BE360 to clarify its anti-osteoporosis activity. BE360 showed a high binding affinity to estrogen receptors (ER), ERalpha and ERbeta. In ovariectomized (OVX) mice, femoral bone volume was markedly reduced and BE360 dose-dependently restored bone loss in OVX mice. However, BE360 did not exhibit any estrogenic activity in the uterus. BE360 also restored bone loss in orchidectomized mice without androgenic action in the sex organs. Therefore, BE360 is a novel selective estrogen receptor modulator (SERM) that may offer a new therapy option for osteoporosis.
authors.affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Hirata
authors.forename: Masaki
authors.initials: M
authors.lastname: Inada
authors.forename: Chiho
authors.initials: C
authors.lastname: Matsumoto
authors.forename: Morichika
authors.initials: M
authors.lastname: Takita
authors.forename: Takumi
authors.initials: T
authors.lastname: Ogawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Endo
authors.forename: Chisato
authors.initials: C
authors.lastname: Miyaura
mesh_terms: D000818:Animals; D001284:Atrophy; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects*; D001895:Boron / Q000737:chemistry*; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D005835:Genitalia / Q000187:drug effects; D008297:Male; D051379:Mice; D014599:Uterus / Q000187:drug effects / Q000473:pathology
chemical_list: C539509:BE360 compound; D001896:Boron Compounds; D020847:Estrogen Receptor Modulators; D001895:Boron