78 zoekresultaten voor “parp inhibitors” in de Publieke website
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Cancer chess: molecular insights into PARP inhibitor resistance
The clinical potential of applying synthetic lethality to cancer treatment is famously demonstrated by the BRCA1/PARP1 paradigm: a tumor specific defect in BRCA1 – a component of the DNA double-strand break (DSB) repair pathway homologous recombination (HR) – results in a remarkable sensitivity to PARP1…
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Discovery of Reversible Monoacylglycerol Lipase Inhibitors
Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.
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Inhibitor discovery of phospholipases and N-acyltransferases
In this thesis an activity-based probe was discovered that could visualize the activity of PLAATs. With an optimized gel-based ABPP assay in hand, screening of a compound library led to the discovery of alpha-ketoamides as a hit for PLAAT3.
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Targeting Human Proteasomes: Substrates, Inhibitors and Prodrugs
Large parts of the research described in this Thesis aims at the development of oligopeptide-masked toxins and their in situ immunoproteasome-mediated activation.
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Small molecule inhibitors of Nicotinamide N-Methyltransferase (NNMT)
NNMT wordt beschouwd als een nieuw potentieel farmacologisch doelwit in de behandeling van een verscheidenheid van kankers, stofwisselingsziekten en andere pathologieën. Het toenemend aantal publicaties waarin de rol van NNMT bij ziekten wordt opgehelderd, heeft op zijn beurt de ontwikkeling van krachtige…
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Inhibitor Selectivity: Profiling and Prediction
Less than 1 in 10 drug candidates that enter phase 1 clinical trials actually gets approved for human use.
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Inhibitors and probes targeting endo-glycosidases
The chemical synthesis of inhibitors and probes targeting endo-glycosidases.
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Development of kinase inhibitors and activity-based probes
Promotor: H.S. Overkleeft, J. Neefjes, Co-promotor: M. van der Stelt
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Precision modeling of breast cancer in the CRISPR era
The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.
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and its derivatives: synthesis and application as beta-glycosidase inhibitors
Promotores: Prof.dr. H.S. Overkleeft, Prof.dr. G.A. van der Marel
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Iminosugars as glucosylceramide processing enzymes inhibitors: design, synthesis and evaluation
This Thesis describes the design, synthesis and evaluation as glycoprocessing enzyme inhibitors of focused libraries of iminosugars.
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Cancer Chess: Molecular Insights into PARP Inhibitor Resistance
Promotie
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Discovery of novel inhibitors to investigate diacylglycerol lipases and α/β hydrolase domain 16A
Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt
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Discovery and development of inhibitors selective for human constitutive proteasome and immunoproteasome active sites
This thesis describes the design and development of subunit‐selective inhibitors of particular catalytically active subunits of human constitutive proteasomes and immunoproteasomes.
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Design and development of conformational inhibitors and activity-based probes for retaining glycosidases
Glycosidases are essential in fundamental biological processes and are responsible for the degradation of most (oligo)saccharides, glycolipids and glycoproteins.
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solution and crystallographic studies of the Sso10a2 and human C1 inhibitor protein
Promotor: Prof.dr. J.P. Abrahams, Co-Promotor: N.S. Pannu
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candidate || Identification and characterization of small molecule inhibitors of type VII protein secretion systems (1.0 fte)
Wiskunde en Natuurwetenschappen, Leids Instituut voor Chemisch Onderzoek (LIC)
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PhD candidate || Identification and characterization of inhibitors of carbohydrate modifying enzymes to generate a new type of anti-bacterial
Wiskunde en Natuurwetenschappen, Leids Instituut voor Chemisch Onderzoek (LIC)
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PhD student, to identify and characterize inhibitors of carbohydrate modifying enzymes to generate a new type of anti-viral molecule
Wiskunde en Natuurwetenschappen, Leids Instituut voor Chemisch Onderzoek (LIC)
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Targeted Therapy for Triple-Negative Breast Cancer
The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.
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Synthetic Methodology Towards ADP-Ribosylation Related Molecular Tools
Phosphorylation affects all four major biomolecules – proteins, lipids, carbohydrates and nucleic acids – and plays a pivotal role in the most fundamental cellular functions.
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Cyclophellitol analogues for profiling of exo- and endo-glycosidases
To this day, all cyclophellitol-based inhibitors and ABPs have been close analogues of their natural substrate counterparts. As a result, these probes showed high selectivity towards their target glycosidases.
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Chemical tools to monitor and control proteasome activities
Promotores: H.S. Overkleeft; G.A. van der Marel Co-Promotor: B.I. Florea
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Jeroen CodeeWiskunde en Natuurwetenschappen
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Fluorescence Polarization Activity-Based Protein Profiling on Retaining Glycosidases
Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.
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How Electrostatic Interactions Drive Nucleosome Binding of RNF168 & PSIP1
The studies presented in the work show the potential of the integrative use of biophysical data in defining the structural basis of protein interactions.
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Hermen OverkleeftWiskunde en Natuurwetenschappen
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Activity-based protein profiling of diacylglycerol lipases
Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt
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Illuminating N-acylethanolamine biosynthesis with new chemical tools
In this thesis, the discovery and optimization is described of chemical tools to study the N-acylethanolamine (NAE) biosynthetic pathway.
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Inhibitor Selectivity: Profiling and Prediction
Promotie
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Systems pharmacology of the endocannabinoid system
In this thesis, a system pharmacology approach, integrating metabolomics, pharmacology and chemical biology, was applied to understand and modulate the endocannabinoid system across different model systems (cells, zebrafish, mice and humans).
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Discovery of Reversible Monoacylglycerol Lipase Inhibitors
Promotie
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Inhibitor discovery of phospholipases and N-acyltransferases
Promotie
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Small-molecule inhibitors of bacterial metallo-β-lactamases
Promotie
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Targeting Human Proteasomes: Substrates, Inhibitors and Prodrugs
Promotie
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Direct and two-step activity-based profiling of proteases and glycosidases
Promotores: Prof.dr. H.S. Overkleeft, Prof.dr. G.A. van der Marel
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Resistance to PARP inhibition by DNA damage response alterations in BRCA1/2-deficient tumors
Promotie
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Klein molecuul gaat uitzaaien tumorcellen tegen
Leidse chemici wisten met collega’s in York en Israël een molecuul te maken dat de weefselstructuur om een tumor heen steviger houdt. Zo kunnen losse tumorcellen niet zo makkelijk uitzaaien. De onderzoekers hebben al patent op het molecuul aangevraagd, maar gebruik hiervan bij patiënten is nog onzeker.…
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Chemical tools to modulate endocannabinoid biosynthesis
Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt
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The use of activity based protein profiling to study proteasome biology
Promotor: H.S. Overkleeft, Co-Promotor: B.I. Florea
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Chemical genetic approaches for target validation
Drug development is a time- and resource-consuming process that starts with the discovery and validation of a (protein) target that contributes to pathogenesis or disease progression.
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The synthesis of mannose-derived bioconjugates and enzyme inhibitors
Promotie
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Peptide-based probes for protein N-Methyltransferases
The work described in this thesis focuses on the development of linear or cyclized peptide probes against protein N-methyltransferases to characterize their specific binding behavior, providing further binding details for inhibitory activity study.
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The quest for broad-spectrum coronavirus inhibitors
Promotie
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Iminosugars as glucosylceramide processing enzyme inhibitors: design, synthesis and application
Promotie
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Small Molecule Inhibitors of Nicotinamide N-Methyltransferase (NNMT)
Promotie
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Development of kinase inhibitors and activity based probes
Promotie
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Discovery of FLT3 inhibitors for the treatment of acute myeloid leukemia
Promotie
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LACDR in de prijzen bij FIGON Dutch Medicine Days
Tijdens de Dutch Medicine Days viel het Leiden Academic Centre for Drug Research (LACDR) maar liefst drie keer in de prijzen. Bas Goulouze won de PhD Prize voor beste promovendus, Natalia Ortiz Zacarías en Huub Sijben mochten beiden een posterprijs in ontvangst nemen. 'Wetenschappers moeten in staat…
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Discovery of novel inhibitors to investigate diacylglycerol lipases and α/β hydrolase domain 16A
Promotie