Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure of JW-1-60A, we will synthesize a series of its analogs and investigate their selectivity against other kinases in the future.
","abstract_html":"<p>Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure of JW-1-60A, we will synthesize a series of its analogs and investigate their selectivity against other kinases in the future.</p>","abstract_has_math":false,"creators":["Wu, Xiaoxin"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Thesis","degree_discipline":"Pharmaceutical Sciences","degree_department":null,"school":null,"contributors":["Wei Li, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-05-01T07:00:00Z","date_published":"2016-05-01T07:00:00Z","updated_at":"2026-07-24T05:00:23Z","subjects":["JW-1-61A","PKCζ","Structure-based modification","Virtual Screening","Chemical and Pharmacologic Phenomena","Diseases","Endocrine System Diseases","Medical Sciences","Medicinal and Pharmaceutical Chemistry","Medicine and Health Sciences","Pharmaceutics and Drug Design","Pharmacy and Pharmaceutical Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/389","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Wei Li, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Wu, Xiaoxin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-06-23T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmaceutical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["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":["JW-1-61A","PKCζ","Structure-based modification","Virtual Screening","Chemical and Pharmacologic Phenomena","Diseases","Endocrine System Diseases","Medical Sciences","Medicinal and Pharmaceutical Chemistry","Medicine and Health Sciences","Pharmaceutics and Drug Design","Pharmacy and Pharmaceutical Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/389"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure of JW-1-60A, we will synthesize a series of its analogs and investigate their selectivity against other kinases in the future.
"]},{"key":"dc:title","label":"Title","values":["Hit Identification for PKCζ Inhibitors: Structure-Based Optimization, Virtual Screening, and Biological Evaluation"]}]}],"canonical_facts":{"dc:contributor":["Wei Li, Ph.D."],"dc:creator":["Wu, Xiaoxin"],"dc:date.available":["2016-06-23T07:00:00Z"],"dc:description.abstract":["Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure of JW-1-60A, we will synthesize a series of its analogs and investigate their selectivity against other kinases in the future.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/389"],"dc:subject":["JW-1-61A","PKCζ","Structure-based modification","Virtual Screening","Chemical and Pharmacologic Phenomena","Diseases","Endocrine System Diseases","Medical Sciences","Medicinal and Pharmaceutical Chemistry","Medicine and Health Sciences","Pharmaceutics and Drug Design","Pharmacy and Pharmaceutical Sciences"],"dc:title":["Hit Identification for PKCζ Inhibitors: Structure-Based Optimization, Virtual Screening, and Biological Evaluation"],"thesis:degree_discipline":["Pharmaceutical Sciences"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T05:00:23Z"}