Chemical Probes of Rapid Estrogen Signaling in Breast Cancer Treatment and Chemoprevention

摘要: Abstract : The goal of this project was to design new chemical tools selectively probe the molecular mechanisms action rapid estrogen receptor and their relevance breast cancer drugs like tamoxifen. Over course project, we synthesized tested approximately 15 modulators, some with novel activity in terms both classic transcriptional response modulation. We discovered that structure relationship for responses is different than SAR required regulation, but could not be separated from a metabolite tamoxifen, called endoxifen, which appears major bioactive tamoxifen women. This work also resulted letter FDA concerning possible drug interactions between women taking certain antidepressants. made polymer-based conjugate 4-hydroxytamoxifen only shows great uptake into ER positive cells, antiproliferative against antiestrogen sensitive antiestrogen- resistant cell lines. are currently trying translate unexpected finding experimental therapeutics treatment tamoxifen-resistant cancer, an urgent need patients.