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Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male.

Original publication

DOI

10.1016/j.bbrc.2016.07.027

Type

Journal article

Journal

Biochem Biophys Res Commun

Publication Date

09/09/2016

Volume

478

Pages

279 - 285

Keywords

Androgen, Bone mass, Carborane compound, Estrogen, Orchidectomized mice, Osteoporosis, Selective androgen receptor modulator, Androgens, Animals, Bone and Bones, Boranes, Dose-Response Relationship, Drug, Female, Gonads, Humans, Male, Mice, Mice, Inbred Strains, Orchiectomy, Osteoporosis, Ovariectomy, Receptors, Androgen, Receptors, Estrogen, Treatment Outcome