Plasminogen activator inhibitor (PAI-1) is a member of the serine protease inhibitor (serpin) family of proteins, which inhibits certain serine proteases, such as tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), and thus is a primary regulator of fibrinolysis, the process that results in breakdown of blood clots. PAI-1 also exhibits effects on various human ailments including atherosclerosis, stroke and diabetes, with which high levels of PAI-1 have been associated. The goal of this research study is to design novel, potent, and specific small molecule inhibitors of PAI-1. The structural intricacy of the PAI-1 allows for multiple prospective binding sites. This research study explores the synthesis and screening of biological activity of various structural analogues of the lead molecule I-26, which was identified through high-throughput screening. It was hypothesized that the structural alterations of the lead molecule would affect the potency of PAI-1 inhibitor. The design rationale, synthesis and structure-activity relationships of novel small molecule inhibitors of PAI-1 are discussed.
","abstract_html":"<p>Plasminogen activator inhibitor (PAI-1) is a member of the serine protease inhibitor (serpin) family of proteins, which inhibits certain serine proteases, such as tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), and thus is a primary regulator of fibrinolysis, the process that results in breakdown of blood clots. PAI-1 also exhibits effects on various human ailments including atherosclerosis, stroke and diabetes, with which high levels of PAI-1 have been associated. The goal of this research study is to design novel, potent, and specific small molecule inhibitors of PAI-1. The structural intricacy of the PAI-1 allows for multiple prospective binding sites. This research study explores the synthesis and screening of biological activity of various structural analogues of the lead molecule I-26, which was identified through high-throughput screening. It was hypothesized that the structural alterations of the lead molecule would affect the potency of PAI-1 inhibitor. The design rationale, synthesis and structure-activity relationships of novel small molecule inhibitors of PAI-1 are discussed.</p>","abstract_has_math":false,"creators":["Guntaka, Naga Sandhya"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Campus Only Thesis","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Cory Emal, PhD, Chair","Harriet Lindsay, PhD","Deborah Heyl-Clegg, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-07-12T07:00:00Z","date_published":"2013-07-12T07:00:00Z","updated_at":"2026-07-24T02:17:06Z","subjects":["fibrinolysis","molecules","plasminogen","Chemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://commons.emich.edu/theses/622","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Cory Emal, PhD, Chair","Harriet Lindsay, PhD","Deborah Heyl-Clegg, PhD"]},{"key":"dc:creator","label":"Author","values":["Guntaka, Naga Sandhya"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-01-14T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Campus Only Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["fibrinolysis","molecules","plasminogen","Chemistry"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://commons.emich.edu/theses/622"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Plasminogen activator inhibitor (PAI-1) is a member of the serine protease inhibitor (serpin) family of proteins, which inhibits certain serine proteases, such as tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), and thus is a primary regulator of fibrinolysis, the process that results in breakdown of blood clots. PAI-1 also exhibits effects on various human ailments including atherosclerosis, stroke and diabetes, with which high levels of PAI-1 have been associated. The goal of this research study is to design novel, potent, and specific small molecule inhibitors of PAI-1. The structural intricacy of the PAI-1 allows for multiple prospective binding sites. This research study explores the synthesis and screening of biological activity of various structural analogues of the lead molecule I-26, which was identified through high-throughput screening. It was hypothesized that the structural alterations of the lead molecule would affect the potency of PAI-1 inhibitor. The design rationale, synthesis and structure-activity relationships of novel small molecule inhibitors of PAI-1 are discussed.
"]},{"key":"dc:title","label":"Title","values":["Generation of novel small molecules as inhibitors of plasminogen activator inhibitor-1"]}]}],"canonical_facts":{"dc:contributor":["Cory Emal, PhD, Chair","Harriet Lindsay, PhD","Deborah Heyl-Clegg, PhD"],"dc:creator":["Guntaka, Naga Sandhya"],"dc:date.available":["2016-01-14T08:00:00Z"],"dc:description.abstract":["Plasminogen activator inhibitor (PAI-1) is a member of the serine protease inhibitor (serpin) family of proteins, which inhibits certain serine proteases, such as tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), and thus is a primary regulator of fibrinolysis, the process that results in breakdown of blood clots. PAI-1 also exhibits effects on various human ailments including atherosclerosis, stroke and diabetes, with which high levels of PAI-1 have been associated. The goal of this research study is to design novel, potent, and specific small molecule inhibitors of PAI-1. The structural intricacy of the PAI-1 allows for multiple prospective binding sites. This research study explores the synthesis and screening of biological activity of various structural analogues of the lead molecule I-26, which was identified through high-throughput screening. It was hypothesized that the structural alterations of the lead molecule would affect the potency of PAI-1 inhibitor. The design rationale, synthesis and structure-activity relationships of novel small molecule inhibitors of PAI-1 are discussed.
"],"dc:identifier":["https://commons.emich.edu/theses/622"],"dc:subject":["fibrinolysis","molecules","plasminogen","Chemistry"],"dc:title":["Generation of novel small molecules as inhibitors of plasminogen activator inhibitor-1"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Campus Only Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T02:17:06Z"}