Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma.
Article Details
- CitationCopy to clipboard
Chao EY, Collins JL, Gaillard S, Miller AB, Wang L, Orband-Miller LA, Nolte RT, McDonnell DP, Willson TM, Zuercher WJ
Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRgamma.
Bioorg Med Chem Lett. 2006 Feb 15;16(4):821-4. Epub 2005 Nov 22.
- PubMed ID
- 16307879 [ View in PubMed]
- 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.