{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/105125"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/105125","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Discovery and biological evaluation of ferroptocide","abstract":"The chemical diversification of natural products provides a robust and general method for creation of stereochemically complex and structurally diverse small molecules. The resulting compounds have physicochemical traits different from those in most screening collections, and as such are a rich source for biological discovery. Herein, we subject the complexity-to-diversity library of compounds to an anticancer phenotypic screen. This effort resulted in identification of an active class of compounds derived from pleuromutilin natural product. Biological evaluation identified the novel compound ferroptocide, a small molecule that rapidly and robustly induces ferroptotic death of cancer cells. Target identification efforts and CRISPR knockout studies reveal that ferroptocide has a different target from other known pro-ferroptotic agents; it is an inhibitor of thioredoxin, a key component of the thioredoxin antioxidant system in the cell. Ferroptocide shows the ability to positively modulate the immune system in a murine model of breast cancer and will be a useful tool to study the utility of pro-ferroptotic agents for treatment of cancer.","abstract_html":"The chemical diversification of natural products provides a robust and general method for creation of stereochemically complex and structurally diverse small molecules. The resulting compounds have physicochemical traits different from those in most screening collections, and as such are a rich source for biological discovery. Herein, we subject the complexity-to-diversity library of compounds to an anticancer phenotypic screen. This effort resulted in identification of an active class of compounds derived from pleuromutilin natural product. Biological evaluation identified the novel compound ferroptocide, a small molecule that rapidly and robustly induces ferroptotic death of cancer cells. Target identification efforts and CRISPR knockout studies reveal that ferroptocide has a different target from other known pro-ferroptotic agents; it is an inhibitor of thioredoxin, a key component of the thioredoxin antioxidant system in the cell. Ferroptocide shows the ability to positively modulate the immune system in a murine model of breast cancer and will be a useful tool to study the utility of pro-ferroptotic agents for treatment of cancer.","abstract_has_math":false,"creators":["Llabani, Evijola"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Hergenrother, Paul J.","Chan, Jefferson","van der Donk, Wilfred","Zimmerman, Steven C."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-08-23T20:44:27Z","date_published":"2019-08-23T20:44:27Z","updated_at":"2026-07-22T22:24:44Z","subjects":["ferroptosis, thioredoxin"],"languages":["en"],"rights":["Copyright Evijola Llabani 2019"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/105125","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hergenrother, Paul J.","Chan, Jefferson","van der Donk, Wilfred","Zimmerman, Steven C."]},{"key":"dc:creator","label":"Author","values":["Llabani, Evijola"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-08-23T20:44:27Z","2021-08-24T09:15:28Z","2019-01-16","2019-05"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["ferroptosis, thioredoxin"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright Evijola Llabani 2019"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/105125"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The chemical diversification of natural products provides a robust and general method for creation of stereochemically complex and structurally diverse small molecules. The resulting compounds have physicochemical traits different from those in most screening collections, and as such are a rich source for biological discovery. Herein, we subject the complexity-to-diversity library of compounds to an anticancer phenotypic screen. This effort resulted in identification of an active class of compounds derived from pleuromutilin natural product. Biological evaluation identified the novel compound ferroptocide, a small molecule that rapidly and robustly induces ferroptotic death of cancer cells. Target identification efforts and CRISPR knockout studies reveal that ferroptocide has a different target from other known pro-ferroptotic agents; it is an inhibitor of thioredoxin, a key component of the thioredoxin antioxidant system in the cell. Ferroptocide shows the ability to positively modulate the immune system in a murine model of breast cancer and will be a useful tool to study the utility of pro-ferroptotic agents for treatment of cancer.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2021-05-01","The student, Evijola Llabani, accepted the attached license on 2019-01-11 at 17:15.","The student, Evijola Llabani, submitted this Dissertation for approval on 2019-01-11 at 17:32.","This Dissertation was approved for publication on 2019-01-16 at 09:33.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13354 on 2019-08-22 at 16:19:41","Made available in DSpace on 2019-08-23T20:44:27Z (GMT). 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The resulting compounds have physicochemical traits different from those in most screening collections, and as such are a rich source for biological discovery. Herein, we subject the complexity-to-diversity library of compounds to an anticancer phenotypic screen. This effort resulted in identification of an active class of compounds derived from pleuromutilin natural product. Biological evaluation identified the novel compound ferroptocide, a small molecule that rapidly and robustly induces ferroptotic death of cancer cells. Target identification efforts and CRISPR knockout studies reveal that ferroptocide has a different target from other known pro-ferroptotic agents; it is an inhibitor of thioredoxin, a key component of the thioredoxin antioxidant system in the cell. Ferroptocide shows the ability to positively modulate the immune system in a murine model of breast cancer and will be a useful tool to study the utility of pro-ferroptotic agents for treatment of cancer.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2021-05-01","The student, Evijola Llabani, accepted the attached license on 2019-01-11 at 17:15.","The student, Evijola Llabani, submitted this Dissertation for approval on 2019-01-11 at 17:32.","This Dissertation was approved for publication on 2019-01-16 at 09:33.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13354 on 2019-08-22 at 16:19:41","Made available in DSpace on 2019-08-23T20:44:27Z (GMT). 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