208 search results for “kinase inhibitors” in the Public website
-
Noonan and LEOPARD syndrome in zebrafish: molecular mechanisms and cardiac development
Promotor: Prof.dr. J. den Hertog
-
The use of activity based protein profiling to study proteasome biology
Promotor: H.S. Overkleeft, Co-Promotor: B.I. Florea
-
Relative quantification of proteasome activity by activity-based protein profiling and LC-MS/MS
Activity-based protein profiling (ABPP) is a functional proteomics technique for directly monitoring the expression of active enzymes in cell extracts and living cells. The technique relies on irreversible inhibitors equipped with reactive groups (warheads) that covalently attach to the active site…
-
Intercellular Skin Barrier Lipid Composition and Organization in Netherton Syndrome Patients
Netherton Syndrome (NTS) is a rare genetic skin disease caused by mutations in the serine protease inhibitor Kazal-type 5 gene, which encodes the lympho-epithelial Kazal-type-related inhibitor. NTS patients have a profound impaired skin barrier function. Because SC lipids play a crucial role in the…
-
Alkynes in Covalent Enzyme Inhibitors: Down the Kinetic Rabbit Hole
PhD defence
-
700,000 euros for the fight against aggressive breast cancer
To inhibit proteins that contribute to the growth of aggressive cancer cells, that’s the plan of Professor Bob van de Water and his team. They will receive over 700,000 euros from the KWF Dutch Cancer Society for their research. Researcher Maaike Vreeswijk and pathologist Danielle Cohen are affiliated…
-
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.
-
Lipid signaling in brain diseases
Multiple Sclerosis, Parkinson’s and Alzheimer’s disease are the most common neurodegenerative disorders. Unfortunately, no effective treatments are currently available to halt the progression of these neuroinflammatory diseases [1].
-
Chemical biology of glucosylceramide metabolism: fundamental studies and clinical applications for Gaucher disease
How can we develop new chemical biology tools and approaches to understand and interfere with glucosylceramide metabolism in relation to Gaucher disease?
-
Cryo Electron Tomography Studies On Bacterial Chemosensory Arrays
Bacterial chemosensory arrays are protein assemblies that are the key structural and functional component for motile bacteria to sense their internal or environmental chemical signals.
-
Drug Discovery & Safety
In the research programme Drug Discovery & Safety, we are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.
-
Knowledge of DNA repair in the fight against tumour cells
What is the most effective way to eliminate tumour cells? The DNA repair mechanism could play an important role in increasing the effectiveness of chemotherapy in the fight against cancerous cells. If we are to influence this mechanism, we need fundamental knowledge about how the mechanism works.
-
Exposed to events that never happen: Genaralized unsafety and prolonged psysiological stress responses
The aims of the project are to: further clarify 'inhibition by safety'; explore and describe all possible sagety factors, with a special focus on the primary human safety source: social connectedness; reviewing prolonged stress responses without stressors.
-
Topic: Stress and stress-related disorders
The precise psychobiological mechanisms leading to chronic physiological stress responses have not been sufficiently explained, although stress is a major risk factor for disease and early death. A problem for conventional stress theory is that most of these responses seem to occur in situations without…
-
Leiden University strengthens its focus on Chemical Biology and Medicinal Chemistry with seven new group leaders
Tackling key challenges of Chemical Biology and Medicinal Chemistry to aid drug discovery is one of the focus areas of Leiden University. To this end, the Leiden Early Drug Discovery & Development network (LED3) was established by the Leiden Institute of Chemistry (LIC), the Institute of Biology Leiden…
-
Cancer pathogenesis and therapy
With cancer, a person’s body cells grow uncontrollably. Putting together a detailed picture of how this comes about makes it possible to develop efficient therapies. Researchers at the Leiden University Medical Centre (LUMC) and Leiden University are working together to gain a better understanding…
-
Small molecule prevents tumour cells from spreading
Leiden chemists, together with colleagues at the University of York (UK) and Technion (Israel) have discovered a small, sugar-like molecule that maintains the integrity of tissue around a tumour during cancer. This molecule prevents tumour cells from spreading from the primary cancer site to colonise…
-
Research
An overview of the research at the Cancer Dug Target Discovery group.
-
Novel immunomodulatory drugs for tuberculosis treatment
Can drugs that target host signaling pathways be used to eradicate antibiotic-resistant bacteria?
-
Optogenetic activation of intracellular adenosine A2A receptor signaling in the hippocampus is sufficient to trigger CREB phosphorylation and
Source: Mol Psychiatry (2015)
-
Research
The research conducted at the Leiden Academic Centre for Drug Research is clustered within the divisions of BioTherapeutics, Drug Discovery & Safety and Systems Biomedicine and Pharmacology, and the Metabolomics and Analytics Centre.
-
Using functional genetic screens to understand and overcome PARP inhibitor resistance
PhD defence
-
Classical conditioning to improve immunotherapy in cancer
Can the conditioning paradigm be used for checkpoint inhibition cancer treatment?
-
Ultrasensitive in situ visualization of active glucocerebrosidase molecules
Deficiency of glucocerebrosidase (GBA) underlies Gaucher disease, a common lysosomal storage disorder. Carriership for Gaucher disease has recently been identified as major risk for parkinsonism. Presently, no method exists to visualize active GBA molecules in situ. We here report the design, synthesis…
-
Protein arginine methyltransferases as modulators of lipid metabolism and inflammation and the relevance for atherosclerosis
Acute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from atherosclerosis, a progressive condition characterized by the accumulation of lipids, immune cells, and fibrous…
-
Antibiotic Discovery: From mechanistic studies to target ID
The investigations described in this thesis lay out strategies aimed at advancing antibiotic research and development. The examples presented revolve around two main approaches: understanding drug-target interactions and target identification.
-
Novel Immune Cell-Based Therapies for Atherosclerosis
Promotor: Prof.dr. J. Kuiper, Co-Promotor: S.C.A. de Jager
-
Applications for activity-based probes in biomedical research on glycosidases
Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.
-
Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition
Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo.
-
Visualization of Vitamin A Metabolism
Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.
-
Sensing Transport
Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.
-
Immunity in atherosclerosis: novel assays, biomarkers and therapeutic approaches
Atherosclerosis is a progressive disease resulting in the formation of an arterial plaque. Despite lipid lowering, recurrent cardiovascular events remain a risk. While atherosclerosis is primarily lipid-driven, the immune system plays a critical role in the pathophysiology.
-
Macromolecular Biochemistry
Macromolecular Biochemistry is a section of the Leiden Institute of Chemistry at Leiden University, comprising the PIs Marcellus Ubbink, Remus Dame, Aimee Boyle, Lars Jeuken and Anne Wentink.
-
Design and synthesis of metal-based chemotherapeutic agents for targeted DNA interactions or DNA repair pathway modulation
The research presented in this thesis explores the chemotherapeutic potential of metal-based compounds as chemotherapy agents, with an initial focus on the synthesis and DNA interaction studies of platinum and palladium compounds utilizing the [Pt(bapbpy)]2+ scaffold. The study identifies intercalation…
-
discovery of BET bromodomains as the target of Hedgehog Pathway Inhibitor-1
Lecture
-
Activity-Based Proteasome Profiling
Promotor: H.S. Overkleeft, Co-promotor: B.I. Florea
-
Grants & Awards
Grants awarded to molecular physiology research
-
Regulation of actomyosin contraction as a driving force of invasive lobular breast cancer
In this thesis, we used genetically engineered mouse models and a variety of cell-culture based assays to identify genes and pathways that are involved in the development and treatment of invasive lobular carcinoma (ILC).
-
Membrane Fusion Mediated Intracellular Delivery of Lipid Bilayer Coated Mesoporous Silica Nanoparticles
Alexander Kros and co-workers describe how mesoporous silica nanoparticles (MSNs) are delivered into cells via membrane fusion thereby omitting endocytosis pathways. Fusion is induced by a pair of complementary coiled-coil lipopeptides inserted into the membrane of cells and in the bilayer of lipid-coated…
-
When structure-affinity relationships meet structure-kinetics relationships: 3-((Inden-1-yl)amino)-1-isopropyl-cyclopentane-1-carboxamides as
Source: Eur J Med Chem (2015)
-
Using insertional mutagenesis to identify breast cancer drivers and therapy resistance genes in mice
In this thesis, we used genetically engineered mouse models to identify genes and pathways that are involved in ILC formation and in the development of resistance to FGFR-targeted therapy.
-
Chemical biology of sphingolipids: fundamental studies and clinical applications
Overkleeft
-
Reedijk Symposium 2024
Conference
-
Key publications
Key publications of the Cardiovascular Pharmacology group
-
Computational Drug Discovery
Research in this group, headed by Gerard van Westen, focusses on computational methods integrated in different parts of the drug discovery process. More specifically, topics include innovative treatments for cancer, selectivity modeling, translational research, allosteric modulation, drug resistance…
-
Collaborative and effective drug development
There are many complex links in the chain that provides patients with new drugs: from fundamental science, to clinical tests, to production. The entire chain can be found in Leiden. Leiden University, the Leiden University Medical Center (LUMC) and the businesses at the Leiden Bio Science Park (LBSP)…
-
Bio-organic Synthesis
The research in the Biosyn group is focused on the design, synthesis and function of the four major types of biomolecules: nucleic acids, carbohydrates, peptides and lipids and hybrid structures thereof. These biomolecules and their derivatives are used in drug discovery and chemical biology, to develop…
-
PhD: Targeting electron transport chain in Listeria monocytogenes for novel antibiotic development
Science, Leiden Institute of Chemistry (LIC)
-
Leiden researchers discover genes that affect spread of breast cancer
Researchers at Leiden University have mapped genes that cause breast cancer cells to migrate. The Leiden toxicologists Professor Bob van de Water, Dr Wies van Roosmalen, Dr Sylvia E. Le Dévédec and colleagues studied 1500 individual genes. They found eight, including the SRPK1 gene, that regulate the…
-
Reflect react and interact
The roles of shame, guilt and social access in adolescent aggression