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.
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Showing 1 to 13 of 13 for “"proteolysis-targeting chimeras"”.
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Induced Degradation of G-Protein-Coupled Receptors Through Proteolysis Targeting Chimeras
… roles in cancer progression. TPD methods include proteolysis targeting chimeras (PROTACs), which are heterobifunctional molecules where one end has a ligand for the protein-of-interest (POI), and the other end has an E3 ligase recruiting ligand. PROTACs take advantage of the ubiquitin-proteasome …
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Cellular Determinants Of AURKA Degradation By Small Molecule Proteolysis-Targeting Chimeras
In recent years the development of proteolysis-targeting chimeras (PROTACs) has enhanced the field of ubiquitin signalling through advancing therapeutic targeted protein degradation (TPD) strategies and generating tools to explore the ubiquitin landscape. However, the cellular factors that modulate …
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Proteolysis targeting chimeras for the directed ubiquitination of the androgen receptor
Proteolysis targeting chimeras (PROTACs) are an emerging field of therapeutics and promising potential drug candidates. PROTACs consist of a target protein binder connected via a linker to an E3 ligase binder. PROTACs hijack the ubiquitin proteasome system to degrade the target protein in a …
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Novel Proteolysis Targeting Chimeras for the targeted degradation of the protein kinase CK2
… prolonged suppression of CK2 activity. PROTACs (Proteolysis Targeting Chimeras) represent a novel therapeutic strategy that can induce target degradation through the 26S proteasome, offering potential advantages in potency, selectivity, and prolonged biological activity. The aim of this project …
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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 …
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The Design, Synthesis and in vitro Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Degradation of Protein Arginine Methyltransferase 1
… cancer cells to other treatments. Therefore, targeting PRMT1 is a promising therapeutic strategy in cancer treatment. Published inhibitors for PRMT1 show poor selectivity and dose-limiting toxicities that have precluded their translation to the clinic. The degradation of PRMT1 using a PROTAC …
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Developing Computational Methods in Proximity Pharmacology for Enzyme Discovery, PROTAC Screening, and Conformational Space Exploration
… to target degradation. These compounds, called Proteolysis Targeting Chimeras (PROTACs), have shown clinical promise, with two currently in Phase 3 trials. Beyond degradation, the field of proximity pharmacology explores the recruitment of other enzymes, such as kinases, to induce …
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Broad-spectrum antivirals against coronavirus using natural products and drug repurposing strategies
… antiviral profiles. Chapter five shifts to host-targeting strategies through the repurposing of PROTACs (Proteolysis-Targeting Chimeras). Originally developed for oncology, these bifunctional molecules were assessed for their ability to degrade key host proteins exploited by coronaviruses during …
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Chemical Tools for Exploring Metabolite Interactions with Nuclear Receptors and Beyond
… we describe efforts towards the combined use of proteolysis-targeting chimeras (PROTACs) and chemical proteomics in target deconvolution studies. We describe the design and synthesis of PROTACs that recruit putative E3 ligases. Overall, the projects described herein underline the utility of …
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Developing Targeted Therapies for T-cell Acute Lymphoblastic Leukemia
… relationship in patients. To develop novel T-ALL targeting approaches, we designed and synthesized a set of proteolysis targeting chimeras (PROTACs) to degrade LCK in T-ALL. Western blotting was used to measure the extent of degradation of LCK and other target proteins by PROTACs. Cell viability …
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Using Heterogeneous Information Sources for Understanding and Predicting Biological Effects of Compounds
… safety profile of new data modalities such as PROteolysis TArgeting Chimeras (PROTACs). In the first chapter, “Probabilistic Random Forest improves bioactivity predictions close to the classification threshold by taking into account experimental uncertainty”, a novel algorithm was evaluated and …
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CHEMICAL APPROACHES TOWARD NEW PERSPECTIVES IN DRUG DISCOVERY: NATURAL PRODUCTS AND BIOACTIVE HITS AS AN INSPIRATION
… compound assemblies, particularly the emerging proteolysis-targeting chimeras (PROTACs), to inspire the design of innovative molecular architectures that can selectively degrade target proteins. The strategic incorporation of bioactive natural compounds into these bivalent frameworks not only …
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A study of novel tools to measure and perturb Aurora Kinase A protein stability
… therapy with kinase inhibitors. Therefore, targeting the stability of the protein could be a better therapeutic strategy, and to this end, the second half of my work aimed to characterise a novel targeted protein degradation tool for AurKA. In establishing a tool to monitor AurKA turnover, I …