University of Tennessee Health Science Center
Hit Identification for PKCζ Inhibitors: Structure-Based Optimization, Virtual Screening, and Biological Evaluation
Abstract
dc:description.abstract<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>
Degree
thesis:*- Name thesis:degree_name
- Master of Science (MS)
- Level thesis:degree_level
- Thesis
- Discipline thesis:degree_discipline
- Pharmaceutical Sciences
- Year dc:date.available
- 2016
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Wu, Xiaoxin
- Contributors dc:contributor
-
- Wei Li, Ph.D.
Subjects
dc:subject × 12Identifiers
dc:identifier.*- Repository record dc:identifier
- https://dc.uthsc.edu/dissertations/389
- OAI identifier oai:identifier
- oai:dc.uthsc.edu:dissertations-1386