Article citationsMore>>
Blizzard, T.A., Morgan, J.D., Chan, W.D., Birzin, E.T., Pai, L.Y., Hayes, E.C., DaSilva, C.A., Mosley, R.T., Yang, Y.T., Rohrer, S.P., DiNinno, F. and Hammond, M.L. (2005) Estrogen receptor ligands. Part 14: Application of novel antagonist side chains to existing platforms. Bioorganic & Medicinal Chemistry Letters, 15, 5124-5128.
doi:10.1016/j.bmcl.2005.08.084
has been cited by the following article:
-
TITLE:
More Stable, More Estrogenic: The SERM-ERα LBD Complex
AUTHORS:
Li Gao, Yaoquan Tu, Leif A. Eriksson
KEYWORDS:
Breast Cancer; Tamoxifen Resistance; Molecular Dynamics Simulations;
Dihydrobenzoxathiin; SERM
JOURNAL NAME:
Journal of Biophysical Chemistry,
Vol.2 No.3,
August
9,
2011
ABSTRACT: Many synthetic selective estrogen receptor modulators (SERMs) have been cocrystallized with the human estrogen receptor α ligand binding domain (ERα LBD). Despite stabilizing the same canonical inactive conformation of the LBD, most SERMs display different ligand-dependent pharmacological profiles. We show here that increased partial agonism of SERMs is associated with increased conformational stability of the SERM-LBD complexes, by investigation of dihydrobenzoxathiin-based SERMs using molecular modelling techniques. Analyses of tamoxifen (TAM) and 4-hydroxytamoxifen (OHT) in complex with the LBD furthermore indicates that the conversion of TAM to OHT increases both the affinity to ERα and the partial agonism of the anti-cancer drug, which provides a plausible explanation of the counterintuitive results of TAM therapy.
Related Articles:
-
Zhen Sun, Heyong Yin, Xiaoming Yu, Xun Sun, Bo Xiao, Yichi Xu, Zhiguo Yuan, Haoye Meng, Jiang Peng, Changlong Yu, Yu Wang, Quanyi Guo, Aiyuan Wang, Shibi Lu
-
C. S. Blesson, Britt Masironi, Lena Sahlin
-
Rifaat Hilal, M. F Shibl, Moteaa El-Deftar
-
Masao Sugamata, Tomomi Ihara, Ichiro Uchiide
-
Pavel Straka, Miroslava Novotná, Petr Buryan, Olga Bičáková