{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/24463"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/24463","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"I. Estrogen receptor-mediated inhibition of inflammatory signaling: Implications for treatment of breast cancer II. Small molecule coactivator-binding inhibitors","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Oldham, Edward D."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Katzenellenbogen, John A.","Baranger, Anne M.","Coates, Robert M.","Gennis, Robert B."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-25T14:25:32Z","date_published":"2011-05-25T14:25:32Z","updated_at":"2026-07-22T22:25:23Z","subjects":["estrogen receptor","breast cancer","anti-inflammatory"],"languages":["en"],"rights":["Copyright 2011 Edward D. 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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.","Item withdrawn by Rebecca Bryant (rabryant@illinois.edu) on 2011-01-03T15:52:09Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 2 Oldham_Edward.docx: 5774464 bytes, checksum: fcdc4f70b2bc7e2d578a50e1d7a22ab2 (MD5) Oldham_Edward.pdf: 4419633 bytes, checksum: 1a911bed006c29b57d1b2bc8f626c04a (MD5)","Made available in DSpace on 2011-05-25T14:25:32Z (GMT). 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