Synthesis and biological characterization of anti-estrogen conjugates
The overall function of estrogen receptor modulators and their role in the signaling of estrogen receptors through non-classical pathways is poorly understood. One possible method to answer to this question is to develop chemical tools to selectively target non-classical ER signaling pathways. The development of molecules that localize to specific subcellular areas offers a potential way to study non-classical ER signaling mechanisms. Conjugation of drugs to macromolecular scaffolds is a well-established strategy to modulate drug properties but stable conjugates have rarely been used to target steroid hormone receptors. Tamoxifen (TAM) is used extensively to treat breast cancer, but the signaling mechanisms associated with TAM are quite complex. In an effort to better understand tamoxifen action in cells and to explore the possibility of targeting nuclear receptors with conjugates, we have developed several polymer and fluorescent conjugates with unexpected cellular activities, and unique localization patterns.
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