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ID: ALA1143314

Journal: Bioorg Med Chem Lett

Title: Bone selective effect of an estradiol conjugate with a novel tetracycline-derived bone-targeting agent.

Authors: Neale JR, Richter NB, Merten KE, Taylor KG, Singh S, Waite LC, Emery NK, Smith NB, Cai J, Pierce WM.

Abstract: In this study a novel bone-targeting agent containing elements of the tricarbonylmethane system of ring A of tetracycline was developed and was shown to bind to the mineral constituent of bone, hydroxyapatite. Conjugation of this bone-targeting agent to estradiol resulted in a bone-targeted estrogen (BTE(2)-A1) with an enhanced ability to bind to hydroxyapatite. In an ovariectomized rat model of osteoporosis a partial separation of the skeletal effects of estradiol from the uterine effects was observed following subcutaneous administration of BTE(2)-A1. This novel bone-targeting estradiol delivery system has the potential to improve the safety profile of estradiol in the treatment of osteoporosis.

CiteXplore: 19117754

DOI: 10.1016/j.bmcl.2008.12.051