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Synthesis of a gefitinib-based chemical probe for mechanism-of-action studies

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posted on 2024-06-25, 04:02 authored by Dean Thomas Marinucci

Protein kinases catalyse the phosphorylation of proteins and are key regulators of cell signalling. Aberrant kinase activity results in malignant disease, and protein kinases are major drug targets as a result. The epidermal growth factor receptor (EGFR) protein kinase is a particularly significant driver of tumorigenesis and a validated drug target for breast and lung cancers. However, EGFR drugs produce deleterious side effects in patients and encounter significant cancer resistance over 18 months. Chemical proteomics converts a drug of interest into a “chemical probe” which is used in tandem with a proteomics workflow to purify and identify protein drug targets from an endogenous context. This project successfully synthesised a light-switchable chemical probe from the drug gefitinib (EGFR inhibitor). This probe is expected to enable future identification of the cellular targets of gefitinib with precision in order to inform the mechanisms underlying its anti-proliferative effects, side effects and resistance in cancer as well as superior design principles for next generation drugs.

History

Table of Contents

1. Introduction -- 2. Experimental -- 3. Results and discussion -- 4. Conclusions & future work -- 5. References -- 6. Supplementary material

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

Master of Research

Department, Centre or School

School of Natural Sciences

Year of Award

2024

Principal Supervisor

Fei Liu

Additional Supervisor 1

Koushik Venkatesan

Rights

Copyright: The Author Copyright disclaimer: https://www.mq.edu.au/copyright-disclaimer

Language

English

Extent

74 pages

Former Identifiers

AMIS ID: 321498

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