Bioorganic & Medicinal Chemistry Letters 2009-02-01

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

文献索引：Bioorg. Med. Chem. Lett. 19 , 680-3, (2009)

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摘要

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.