Date of Award
Master of Science (MS)
Wei Li, Ph.D.
Duane D. Miller, Ph.D. Yongmei Wang, Ph.D.
JW-1-61A, PKCζ, Structure-based modification, Virtual Screening
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.
Wu, Xiaoxin (http://orcid.org/0000-0003-0467-9500), "Hit Identification for PKCζ Inhibitors: Structure-Based Optimization, Virtual Screening, and Biological Evaluation" (2016). Theses and Dissertations (ETD). Paper 389. http://dx.doi.org/10.21007/etd.cghs.2016.0404.