Targeted protein degradation of the Y220C-p53 mutant as a potential anti-cancer strategy

Miller, Hollie (2024) Targeted protein degradation of the Y220C-p53 mutant as a potential anti-cancer strategy. MRes thesis, University of Glasgow.

Abstract

Targeted protein degradation and Proteolysis Targeting Chimeras (PROTACs) in particular, have become an exciting new field in the drug discovery world, with the potential to target previously seen as ‘undruggable’ proteins. With many PROTACs now reaching the clinic, it is clear that these new modalities have the potential to become therapeutically successful and to overcome problems previously observed with traditional small molecule drugs. One of the most frequently mutated proteins in human cancers, p53 has been a particularly challenging drug target for many years. The work presented in this thesis provides a strategy in which to target and degrade the common Y220C p53 mutant by utilising the PROTAC degradation mechanism.

In particular, PROTAC 2 was found to degrade the Y220C p53 mutant at a low micromolar concentration and hence provides insight into the potential these PROTACs hold for the future as potent degraders of target proteins.

• Item Type: Thesis (MRes)
• Qualification Level: Doctoral
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer); R Medicine > RM Therapeutics. Pharmacology
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: France, Dr. David and Huang, Professor Danny
• Date of Award: 2024
• Depositing User: Theses Team
• Unique ID: glathesis:2024-84041
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 19 Jan 2024 15:57
• Last Modified: 19 Jan 2024 15:59
• Thesis DOI: 10.5525/gla.thesis.84041
• URI: https://theses.gla.ac.uk/id/eprint/84041