title: Bone selective effect of an estradiol conjugate with a novel tetracycline-derived bone-targeting agent.
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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Neale
authors.forename: Natali B
authors.initials: NB
authors.lastname: Richter
authors.forename: Kevyn E
authors.initials: KE
authors.lastname: Merten
authors.forename: K Grant
authors.initials: KG
authors.lastname: Taylor
authors.forename: Sujan
authors.initials: S
authors.lastname: Singh
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Waite
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Emery
authors.forename: Ned B
authors.initials: NB
authors.lastname: Smith
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.forename: William M
authors.initials: WM
authors.lastname: Pierce
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D017886:Durapatite / Q000737:chemistry; D004958:Estradiol / Q000737:chemistry*; D004967:Estrogens / Q000737:chemistry; D005260:Female; D010024:Osteoporosis / Q000188:drug therapy*; D010052:Ovariectomy; D011500:Protein Synthesis Inhibitors / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013752:Tetracycline / Q000032:analysis / Q000737:chemistry*
chemical_list: D004967:Estrogens; D011500:Protein Synthesis Inhibitors; D004958:Estradiol; D017886:Durapatite; D013752:Tetracycline