Year: 2018
Type: dissertation
Abstract: The targeted covalent inhibitor (TCI) approach in drug discovery presents many potential benefits to cancer therapy. The goal of this approach is to trigger apoptosis of rapidly dividing tumour cells by covalently binding a therapeutically relevant protein target. Ultimately the goal is to develop personalized treatments that are more effective and less toxic than general chemotherapy. JP-4-94 is a potent covalent investigational cancer therapeutic with promising in vitro and in vivo results. Herein, we describe studies undertaken to further understand the structural mechanisms through which JP-4-94 elicits a cellular response. Specifically, this dissertation will explore the role of π-stacking in conformationally protecting the warhead in JP-4-94 to further optimize its pharmacological properties. Through our findings, a class of potent, second-generation inhibitors has been identified.
Source: TSpace (University of Toronto)
Author: Mariya Bogatchenko
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W3092909647