{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/80748"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/80748","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Discovery and Pharmacological Characterization of Environmental Melatonin Receptor Modulators","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Jones, Anthony; 0000-0002-9954-2816"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Dubocovich, Margarita","Neuroscience"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-10-29T15:39:26Z","date_published":"2019-10-29T15:39:26Z","updated_at":"2026-07-27T19:05:23Z","subjects":["pharmacology","toxicology","neurosciences"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/80748","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dubocovich, Margarita","Neuroscience"]},{"key":"dc:creator","label":"Author","values":["Jones, Anthony; 0000-0002-9954-2816"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-10-29T15:39:26Z","2019","2019-08-23 10:37:20"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmacology","toxicology","neurosciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/80748"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Melatonin targets MT1 and MT2 melatonin receptors that are expressed in brain and peripheral tissues in order to signal “time-of-day” messages for the synchronization of circadian rhythms. In 2017, Popovska-Gorevski et al. demonstrated via in-silico screening paired with competition binding that environmental carbamate insecticides with similar pharmacophores to melatonin, carbaryl and carbofuran, may be human (h) MT1 and MT2 melatonin receptor disruptors based on their affinity for melatonin recombinant receptors. Carbaryl (Ki hMT1 = 3.3 µM, hMT2 = 0.16 µM) and carbofuran (Ki hMT1 = 94 µM, hMT2 = 3.6 µM) are only two of many environmental pollutants identified by in-silico chemical clustering to have a similar structure to melatonin. It is most likely that melatonin receptor modulators with different pharmacological activities than melatonin will be the most disruptive for rhythmic homeostatic processes, such as timekeeping in the suprachiasmatic nucleus or pancreatic insulin release. Therefore, we hypothesized that further screening in-vitro would identify melatonin receptor-specific environmental toxins that exhibit signaling profiles distinct from melatonin. The objectives of this study were to identify environmental melatonin receptor modulators using integrated pharmacoinformatics and competition binding, to determine pharmacological properties of melatonin receptor ligands at hMT1 and hMT2 receptors in-vitro, and to assess the ability of unique environmental melatonin receptor modulators to alter melatonin receptor-mediated processes in target tissues."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Discovery and Pharmacological Characterization of Environmental Melatonin Receptor Modulators"]}]}],"canonical_facts":{"dc:contributor":["Dubocovich, Margarita","Neuroscience"],"dc:creator":["Jones, Anthony; 0000-0002-9954-2816"],"dc:date":["2019-10-29T15:39:26Z","2019","2019-08-23 10:37:20"],"dc:description":["Ph.D.","Melatonin targets MT1 and MT2 melatonin receptors that are expressed in brain and peripheral tissues in order to signal “time-of-day” messages for the synchronization of circadian rhythms. In 2017, Popovska-Gorevski et al. demonstrated via in-silico screening paired with competition binding that environmental carbamate insecticides with similar pharmacophores to melatonin, carbaryl and carbofuran, may be human (h) MT1 and MT2 melatonin receptor disruptors based on their affinity for melatonin recombinant receptors. Carbaryl (Ki hMT1 = 3.3 µM, hMT2 = 0.16 µM) and carbofuran (Ki hMT1 = 94 µM, hMT2 = 3.6 µM) are only two of many environmental pollutants identified by in-silico chemical clustering to have a similar structure to melatonin. It is most likely that melatonin receptor modulators with different pharmacological activities than melatonin will be the most disruptive for rhythmic homeostatic processes, such as timekeeping in the suprachiasmatic nucleus or pancreatic insulin release. Therefore, we hypothesized that further screening in-vitro would identify melatonin receptor-specific environmental toxins that exhibit signaling profiles distinct from melatonin. The objectives of this study were to identify environmental melatonin receptor modulators using integrated pharmacoinformatics and competition binding, to determine pharmacological properties of melatonin receptor ligands at hMT1 and hMT2 receptors in-vitro, and to assess the ability of unique environmental melatonin receptor modulators to alter melatonin receptor-mediated processes in target tissues."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/80748"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["pharmacology","toxicology","neurosciences"],"dc:title":["Discovery and Pharmacological Characterization of Environmental Melatonin Receptor Modulators"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:23Z"}