1YIM

Human estrogen receptor alpha ligand-binding domain in complex with compound 4

Summary for 1YIM

• Entry DOI: 10.2210/pdb1yim/pdb
• Related: 1YIN
• Descriptor: Estrogen receptor, (2R,3R,4S)-3-(4-HYDROXYPHENYL)-4-METHYL-2-[4-(2-PYRROLIDIN-1-YLETHOXY)PHENYL]CHROMAN-6-OL (3 entities in total)
• Functional Keywords: nuclear receptor, transcription factor, er-alpha, antagonist, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Nucleus . Isoform 3: Nucleus. Nucleus: P03372
• Total number of polymer chains: 1
• Total formula weight: 28761.87

Authors

Fitzgerald, P.M.,Sharma, N. (deposition date: 2005-01-12, release date: 2005-07-26, Last modification date: 2024-02-14)

Primary citation

Tan, Q.,Blizzard, T.A.,Morgan, J.D.,Birzin, E.T.,Chan, W.,Yang, Y.T.,Pai, L.Y.,Hayes, E.C.,DaSilva, C.A.,Warrier, S.,Yudkovitz, J.,Wilkinson, H.A.,Sharma, N.,Fitzgerald, P.M.,Li, S.,Colwell, L.,Fisher, J.E.,Adamski, S.,Reszka, A.A.,Kimmel, D.,DiNinno, F.,Rohrer, S.P.,Freedman, L.P.,Schaeffer, J.M.,Hammond, M.L.
Estrogen receptor ligands. Part 10: Chromanes: old scaffolds for new SERAMs.
Bioorg.Med.Chem.Lett., 15:1675-1681, 2005

PubMed Abstract: The discovery, synthesis, and SAR of chromanes as ER alpha subtype selective ligands are described. X-ray studies revealed that the origin of the ER alpha-selectivity resulted from a C-4 trans methyl substitution to the cis-2,3-diphenyl-chromane platform. Selected compounds from this class demonstrated very potent in vivo antagonism of estradiol in an immature rat uterine weight assay, effectively inhibited ovariectomy-induced bone resorption in a 42 days treatment paradigm, and lowered serum cholesterol levels in ovx'd adult rat models. The best antagonists 8F and 12F also exhibited potent inhibition of MCF-7 cell growth and were shown to be estrogen receptor down-regulators (SERDs).

PubMed: 15745820
DOI: 10.1016/j.bmcl.2005.01.046

Experimental method

X-RAY DIFFRACTION (1.9 Å)