I. Estrogen receptor-mediated inhibition of inflammatory signaling: Implications for treatment of breast cancer II. Small molecule coactivator-binding inhibitors

estrogen receptor;breast cancer;anti-inflammatory

Oldham, Edward D.

关键词: estrogen receptor;    breast cancer;    anti-inflammatory;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/24463/Oldham_Edward.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Approximately two-thirds of breast cancers result from overexpression of the estrogen receptor, a ligand-dependent transcription factor. Traditional therapy employs drugs that bind directly to the receptor but do not mediate transcription. Unfortunately most breast cancers develop resistance to these antagonists. The mechanism of this resistance is not fully known. This thesis describes two different approaches to circumventing this resistance.In Chapter 2, the unique anti-proliferative and anti-inflammatory activity of a lead compound, OBHS, is described. A crystal structure of OBHS bound to the estrogen receptor provided the basis for structural and functional analogs of OBHS. These compounds exhibited weaker binding to the estrogen receptor than OBHS; however some displayed comparable anti-inflammatory activity.In Chapter 3, compounds were designed and synthesized in order to inhibit the binding of the estrogen receptor to coactivator proteins that facilitate transcription. We used a peptidomimetic approach to mimic conserved amino acids on the coactivator proteins. Compounds designed in this way did not inhibit the interaction between the estrogen receptor and a coactivator protein.