Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRγ

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

doi:10.1016/j.bmcl.2005.11.030

Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRγ

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

Research output: Contribution to journal › Article › peer-review

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 γ and the classical estrogen receptor α 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 ERRγ LBD confirms the molecular basis of the selectivity.

Original language	English (US)
Pages (from-to)	821-824
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2005.11.030
State	Published - Feb 15 2006
Externally published	Yes

Keywords

ERRγ chemical tool
Orphan nuclear receptor

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRγ. / Chao, Esther Y.H.; Collins, Jon L.; Gaillard, Stéphanie; Miller, Aaron B.; Wang, Liping; Orband-Miller, Lisa A.; Nolte, Robert T.; McDonnell, Donald P.; Willson, Timothy M.; Zuercher, William J.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 4, 15.02.2006, p. 821-824.

Research output: Contribution to journal › Article › peer-review

Chao, Esther Y.H. ; Collins, Jon L. ; Gaillard, Stéphanie ; Miller, Aaron B. ; Wang, Liping ; Orband-Miller, Lisa A. ; Nolte, Robert T. ; McDonnell, Donald P. ; Willson, Timothy M. ; Zuercher, William J. / Structure-guided synthesis of tamoxifen analogs with improved selectivity for the orphan ERRγ. In: Bioorganic and Medicinal Chemistry Letters. 2006 ; Vol. 16, No. 4. pp. 821-824.

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AU - Wang, Liping

AU - Orband-Miller, Lisa A.

AU - Nolte, Robert T.

AU - McDonnell, Donald P.

AU - Willson, Timothy M.

AU - Zuercher, William J.

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