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

Jason R Neale, Natali B Richter, Kevyn E Merten, K Grant Taylor, Sujan Singh, Leonard C Waite, Nicole K Emery, Ned B Smith, Jian Cai, William M Pierce, Jason R Neale, Natali B Richter, Kevyn E Merten, K Grant Taylor, Sujan Singh, Leonard C Waite, Nicole K Emery, Ned B Smith, Jian Cai, William M Pierce, Jason R. Neale, Natali B. Richter, Kevyn E. Merten, K. Grant Taylor, Sujan Singh, Leonard C. Waite, Nicole K. Emery, Ned B. Smith, Jian Cai, William M. Pierce

Index: Bioorg. Med. Chem. Lett. 19 , 680-3, (2009)

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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.