Date of Award

5-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Pharmaceutical Sciences

Track

Medicinal Chemistry

Research Advisor

Wei Li, Ph.D.

Committee

Duane D. Miller, Ph.D. Yongmei Wang, Ph.D.

Keywords

JW-1-61A, PKCζ, Structure-based modification, Virtual Screening

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.

ORCID

http://orcid.org/0000-0003-0467-9500

DOI

10.21007/etd.cghs.2016.0404

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