Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 9 of 9 for “"Proteolysis-targeting chimera (PROTAC)"”.
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Metastatic Reactivation and Progression Result From Fak-Mediated Disruption of Innate Immune Signaling
… Genetic deletion or targeted degradation with proteolysis targeting chimera (PROTAC) of Fak, but not inhibition of its kinase activity, restores interferon production and enhances the sensitivity of incipient and established metastases to Sting agonists and immune checkpoint blockade. These …
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Functional investigation of PERIOD in the mammalian circadian clock
… a series of constitutive overexpression and proteolysis targeting chimera (PROTAC) acute knockdowns. Next, PER2 activity changes over the cellular circadian cycle were assessed through time-resolved mass spectrometry of the PER2 interactome. Finally, CRISPR-mediated gene editing was used to …
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Targeting Transcription Factors in Neuroblastoma: Development of Aurora Kinase A/N-Myc Degraders and ID2 Chemical Probes
… signaling pathways in tumor cells. However, targeting TFs with small molecules is challenging as they frequently lack endogenous ligands or amenable ligandbinding sites. The thesis will discuss our efforts in the development of novel chemical modulators of TFs in neuroblastoma using targeted …
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Modulation of BAZ2 Proteins as a Potential Therapeutic Strategy in Cancer and Neurological Disorders
… " toward target elimination by exploiting PROteolysis Targeting Chimera (PROTAC) technology. This innovative approach allows protein degradation by fostering interactions between an E3 ubiquitin ligase and a POI, effectively directing the ubiquitin-proteasome system to eliminate the target …
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Targeting Protein Degradation to Uncover Novel Oncoprotein Drivers of Acute Leukemia
… this paradigm, small molecule degraders (either Proteolysis Targeting Chimera (PROTAC) or Molecular Glue (MG)) redirect the cell’s endogenous ubiquitin proteasome system and induce ubiquitination of the target protein or non-native substrate of an E3 ligase (neosubstrate) and its subsequent …
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SGK3 activity and regulation in PI3K-Akt pathway inhibitor resistance in breast cancer
… the Ciulli lab, designed and characterised SGK3-PROTAC1, a Proteolysis Targeting Chimera (PROTAC) which targeted SGK3 for specific ubiquitylation by VHL E3 ligase and subsequent proteasomal degradation. I demonstrated by quantitative Mass Spectrometry that SGK3-PROTAC1 mediated degradation was …
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Therapeutic Vulnerabilities of Venetoclax Resistant Chronic Lymphocytic Leukemia and Novel Treatment Strategies Targeting BCL2/BCL-XL
… led to the overall hypothesis of this thesis: co-targeting BCL2 and BCL-XL can effectively overcome VEN resistance in CLL. A major clinical barrier in developing BCL-XL inhibitors is the on-target toxicity to platelets. Therefore, the current thesis focuses on circumventing platelet toxicity with …
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DESIGN, SYNTHESIS AND BIOLOGICAL PROFILING OF NEW COMPOUNDS: INFECTIOUS AND NEURODEGENERATIVE DISEASES AS TARGETS
… commenced with a meticulous exploration of Proteolysis Targeting Chimera (PROTAC) technology as a promising therapeutic avenue. Within the confines of Chapter 1 of my dissertation, I delved into the intricate design and synthesis of dual-action modulators meticulously engineered to …
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Proteolysis-targeting chimeras as a novel strategy for targeting epigenetic mechanisms in Plasmodium falciparum parasites
… development. We therefore proposed the use of Proteolysis-targeting chimeras (PROTACs) that can induce the degradation of a target protein via the cells ubiquitin-proteasome system rather than inhibiting it. Ideally, for PROTACs to be effective in malaria research, they should bind to essential …