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 7 of 7 for “"VHL E3 ligase"”.
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Fragment-based approaches to probe the surface of the VHL E3 ligase
… involved in the control of protein homeostasis, E3 ubiquitin ligases are emerging as interesting targets for the development of chemical probes and drugs. Small-molecule modulation of E3 ligases can provide several advantages over other members of the ubiquitin-proteasome system (UPS), as E3 …
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Induced Degradation of G-Protein-Coupled Receptors Through Proteolysis Targeting Chimeras
… (POI), and the other end has an E3 ligase recruiting ligand. PROTACs take advantage of the ubiquitin-proteasome system (UPS) by forcing a POI in proximity to an E3 ligase through the formation of a ternary complex between the POI, PROTAC, and E3 ligase. Then promoting the transfer …
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Novel Proteolysis Targeting Chimeras for the targeted degradation of the protein kinase CK2
… to Cereblon (CRBN) and Von Hippel–Lindau (VHL) E3-ligase ligands via a linker. The project was split into three stages: development of a synthetic route towards PROTACs; synthesis of PROTAC candidates, and evaluation of their biological activity in vitro. Four VHL-based PROTACs were …
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The Design, Synthesis and in vitro Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Degradation of Protein Arginine Methyltransferase 1
… that comprised a PRMT1 ligand, a linker and an E3-ligase ligand. Ten PROTACs that recruit the VHL E3-ligase and six PROTACs that recruit the CRBN E3-ligase were synthesised. The degradation of PRMT1 was assessed by Western blot and degradation was not observed for the PROTACs synthesised. …
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Protein-based Degrader Strategies against Oncogenic RAS
… conjugated to a small molecule ligand of the VHL E3 ligase, VL1. We confirmed the cytosolic entry of esterified R11.1.6-VL1 and demonstrated efficacy in human cancer cell lines through in vitro studies. Although modest efficacy in RAS degradation and growth inhibition was observed, this …
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SGK3 activity and regulation in PI3K-Akt pathway inhibitor resistance in breast cancer
… 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 highly specific. Rapid, reversible degradation of SGK3 provided a tool for specifically modulating SGK3 …
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Therapeutic Vulnerabilities of Venetoclax Resistant Chronic Lymphocytic Leukemia and Novel Treatment Strategies Targeting BCL2/BCL-XL
… targeting chimera (PROTAC) engages the VHL E3 ligase to degrade BCL2 and BCL-XL via the proteasome while sparing platelets that express low levels of VHL. As validated in leukemia cell lines and primary CLL, WH25244 degrades VEN-resistant forms of <em>BCL2</em> (i.e. mutant and serine 70 …