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Goetz, M.P., Rae, J.M., Suman, V.J., Safgren, S.L., Ames, M.M., Visscher, D.W., Reynolds, C., Couch, F.J., Lingle, W.L., Flockhart, D.A., Desta, Z., Perez, E.A. and Ingle, J.N. (2005) Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. Journal of Clinical Oncology, 23, 9312-9318. doi:10.1200/JCO.2005.03.3266

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.