113 zoekresultaten voor “kinase inhibitor” in de Publieke website
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Discovery of BUB1 kinase inhibitors for the treatment of cancer
The spindle-assembly checkpoint (SAC) is a safety mechanism which secures accurate chromosome segregation during mitosis.
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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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Discovery of FLT3 inhibitors for the treatment of acute myeloid leukemia
The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.
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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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Arabidopsis AGC3 kinases and PIN plasma membrane abundance
The plant hormone auxin plays a central role in the growth and development of plants. Auxin acts in a concentration dependent manner and polar cell-to-cell transport of this hormone determines its distribution in the tissues of plants. This polar auxin transport is mediated by several families of auxin…
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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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Small-molecule inhibitors of bacterial metallo-β-lactamases
The main focus of the thesis is the discovery and development of novel inhibitors of bacterial metallo-β-lactamases (MBLs).
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Inhibitors and probes targeting endo-glycosidases
The chemical synthesis of inhibitors and probes targeting endo-glycosidases.
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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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The role of AGC3 kinases and calmodulins in plant growth responses to abiotic signals
Promotor: Prof.dr. P. Hooykaas, Co-promotor: R. Offringa
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Functions of P38 and ERK kinases in zebrafish early development
Promotor: Prof.dr. H.P. Spaink, Co-promotor: Dr. B.E. Snaar
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Novel factors modulating AGC kinase signaling-controlled polar auxin transport
The PID-directed shift in PIN polarity has been broadly accepted as one of the essential mechanisms for the regulation of auxin transport polarity.
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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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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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Exploring chemical space in covalent and competitive glycosidase inhibitor design
Glycoside hydrolases (glycosidases/GHs) are widely abundant enzymes in all kingdoms of life and are important biocatalysts that catalyze the hydrolysis of glycosidic linkages in oligo/polysaccharides, glycoproteins and glycolipids with tremendous efficiency
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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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Regulation of the arabidopsis AGC kinase PINOID by PDK1 and the microtubule cytoskeleton
Plants, are sessile organisms, have developed strategies to adapt to changes in their environment, in part by altering their growth and development.
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The synthesis of mannose-derived bioconjugates and enzyme inhibitors
Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: J.D.C. Codee
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Discovery of BUB1 kinase inhibitors for the treatment of cancer
Promotie
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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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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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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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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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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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Uncovering vulnerabilities in triple-negative breast cancer
Triple-negative breast cancer (TNBC) constitutes a small subtype (~15%) of breast cancer, but causes the majority of breast cancer-related deaths.
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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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Mario van der SteltWiskunde en Natuurwetenschappen
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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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Jeroen CodeeWiskunde en Natuurwetenschappen
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Osteosarcoma: searching for new treatment options
Promotores: B. van de Water; P. Hogendoorn; J. Bovée Co-Promotor: E.H.J. Danen
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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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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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Modulating the behaviour of pancreatic tumour cells
Promotores: Prof.dr. M.K. Richardson, Prof.dr. H.P. Spaink. Co-promotor: C.P. Bagowski
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Activity-based protein profiling in drug discovery
In the last decades, activity-based protein profiling (ABPP) has emerged as a powerful chemical tool that may aid the ever-challenging drug discovery process.
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Unieke medicijnstructuren vinden met kunstmatige intelligentie en scheikunde
In de zoektocht naar nieuwe medicijnen tegen onder andere kanker heeft een Leids team een nieuwe werkwijze ontwikkeld. Dit stappenplan combineert kunstmatige intelligentie (AI) met moleculair modelleren en is geschikt om onbekende en vernieuwende medicijnstructuren te vinden, zo bewezen de onderzoek…
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Discovery of FLT3 inhibitors for the treatment of acute myeloid leukemia
Promotie
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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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Immune checkpoint inhibitors in mesothelioma
Promotie
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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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Structural characterization of bacterial proteins involved in antibiotic resistance and peptidoglycan biosynthesis
This thesis describes the structural and biochemical characterization of the β-lactamase BlaC from Mycobacterium tuberculosis (Mtb), and the Alr and YlmE proteins from Streptomyces coelicolor A3(2).Mtb is the main cause of tuberculosis.
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Nieuwe techniek geeft chemici ongekende controle in medicijnonderzoek
Leidse chemici hebben een nieuwe techniek ontwikkeld waarmee ze de rol van kinases – een groep eiwitten – kunnen achterhalen in een levende cel. De techniek maakt het eenvoudiger om nieuwe medicijndoelwitten te vinden voor ziektes als kanker en reuma. Het team publiceerde de bevindingen in het vakblad…
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Inhibitor Selectivity: Profiling and Prediction
Promotie
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Dynamics of a β-lactamase
BlaC is the β-lactamase of Mycobacterium tuberculosis. We show that it can recover from inhibition by clavulanic acid and that phosphate helps it do so.