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The Development of Aminopeptidase N Inhibitors as Potential Anti-Cancer Agents

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thesis
posted on 09.10.2019, 04:32 authored by JISOOK LEE
Cancer is an international major health issue that causes millions of deaths worldwide. Metastasis is a complicated biological process of cancer cells that limits the effectiveness of chemotherapeutic agents and surgical approaches to cancer. Aminopeptidase N (APN) is a zinc dependent metallo-aminopeptidase of the M1 family that has been pursued as a crucial target for cancer. Dysregulated APN activity is known to induce metastasis by angiogenesis. The aim of this project is to improve the potency of previously discovered APN inhibitor through structure-based approaches by optimising the binding interactions at the S1 and S1' subsite of APN. Synthesised compounds were evaluated for its inhibitory activities and cellular anti-proliferative activities. Physicochemical and pharmacokinetic properties of potent inhibitors were also determined. Lastly, the binding interactions between potent inhibitors and APN were investigated through molecular modelling studies.

History

Campus location

Australia

Principal supervisor

Peter Scammells

Additional supervisor 1

Sheena McGowan

Additional supervisor 2

Natalie Vinh

Year of Award

2019

Department, School or Centre

Medicinal Chemistry

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Pharmacy and Pharmaceutical Sciences