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  • Title: Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma.
    Author: Chao EY, Collins JL, Gaillard S, Miller AB, Wang L, Orband-Miller LA, Nolte RT, McDonnell DP, Willson TM, Zuercher WJ.
    Journal: Bioorg Med Chem Lett; 2006 Feb 15; 16(4):821-4. PubMed ID: 16307879.
    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.
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