1093097-18-7Relevant articles and documents
Synthesis and biological evaluation of guanylhydrazone coactivator binding inhibitors for the estrogen receptor
LaFrate, Andrew L.,Gunther, Jillian R.,Carlson, Kathryn E.,Katzenellenbogen, John A.
, p. 10075 - 10084 (2008)
Most patients with hormone-responsive breast cancer eventually develop resistance to traditional antiestrogens such as tamoxifen, and this has become a major obstacle in their treatment. We prepared and characterized the activity of a series of 16 guanylhydrazone small molecules that are designed to block estrogen receptor (ER) activity through a non-traditional mechanism, by directly interfering with coactivator binding to agonist-liganded ER. The inhibitory activity of these compounds was determined in cell-based transcription assays using ER-responsive reporter gene and mammalian two-hybrid assays. Several of the compounds gave IC50 values in the low micromolar range. Two secondary assays were used to confirm that these compounds were acting through the proposed non-traditional mode of estrogen inhibitory action and not as conventional antagonists at the ligand binding site.
