- Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma.
Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma.
Bioorganic & medicinal chemistry letters (2005-11-26)
Esther Y H Chao, Jon L Collins, Stéphanie Gaillard, Aaron B Miller, Liping Wang, Lisa A Orband-Miller, Robert T Nolte, Donald P McDonnell, Timothy M Willson, William J Zuercher
PMID16307879
ABSTRACT
The design and synthesis of 4-hydroxytamoxifen (4-OHT) derivatives are described. The binding affinities of these compounds toward the orphan estrogen-related receptor gamma and the classical estrogen receptor alpha demonstrate that analogs bearing hydroxyalkyl groups display improved binding selectivity profiles compared with that of 4-OHT. An X-ray crystal structure of one of the designed compounds bound to ERRgamma LBD confirms the molecular basis of the selectivity.