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Molecular tools for probing signaling networks of the EGFR protein kinase: a thesis submitted in partial fulfilment of the requirements for the degree of Master of Research

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thesis
posted on 28.03.2022, 23:31 by Ivan de Jesus Salazar Estrada
The epidermal growth factor receptor (EGFR) is one of the first and most extensively studied receptor tyrosine protein kinases and a validated drug target. Through protein phosphorylation EGFR orchestrates several signaling pathways that regulate cell growth and proliferation, and aberrant EGFR signaling has been reported in numerous cancer types. Several FDA-approved drugs target the ATP site of EGFR, and new therapeutics are in development that target the signaling partners of oncogenic EGFR. However, resistance is a challenge to overcome, and other EGFR-associated signaling proteins have been shown to confer resistance. Chemical probes may aid the elucidation of EGFR signaling networks for finding improved combination therapies. Here we report the sunthesis of first-generation biotinylated chemical probes 1a-1c targeting EGFR. These probes are based on the 4-aniloquinazoline core structure of gefitinib and erlotinib, two FDA-approved EGFR-targeting drugs. The probes 1a-1c exhibit excellent binding affinities for EGFR (Kd=23-41 nM). These probes are expected to serve as the basis for future development of next-generation multifunctional probes for understanding exogenous EGFR signaling networks.

History

Table of Contents

1. Introduction -- 2. Experimental section -- 3. Results and discussion -- 4. Conclusions and future directions.

Notes

Bibliography: pages 44-50 Empirical thesis.

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

MRes, Macquarie University, Faculty of Science and Engineering, Department of Chemistry and Biomolecular Sciences

Department, Centre or School

Department of Chemistry and Biomolecular Sciences

Year of Award

2015

Principal Supervisor

Fei Liu

Rights

Copyright Ivan de Jesus Salazar Estrada 2015. Copyright disclaimer: http://www.copyright.mq.edu.au

Language

English

Extent

1 online resource (1 online resource (xv, 50, A1-A11 pages)) illustrations (some colour)

Former Identifiers

mq:44503 http://hdl.handle.net/1959.14/1069786