Article citationsMore>>

Blizzard, T.A., DiNinno, F., Chen, H.Y., Kim, S., Wu, J.Y., Chan, W.D., Birzin, E.T., Yang, Y.T., Pal, L.Y., Hayes, E.C., DaSilva, C.A., Rohrer, S.P., Schaeffer, J.M. and Hammond, M.L. (2005) Estrogen receptor ligands. Part 13: Dihydrobenzoxathiin SERAMs with an optimized antagonist side chain. Bioorganic & Medicinal Chemistry Letters, 15, 3912-3916. doi:10.1016/j.bmcl.2005.05.089

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.