208 search results for “kinase inhibitors” in the Public website
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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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Using zebrafish to target the Achilles’ heel of cancer
Exploiting metabolic vulnerabilities to identify anticancer compounds in zebrafish synthetic lethality screens.
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Pursuing new anti-cancer therapy as a team
Cancer is the leading cause of death in the Netherlands, and, with over 100 different types of cancer, it’s not a simple disease. Today, skin, breast, lung, prostate and colon cancer are the most diagnosed forms. Therefore, the discovery and development of new drugs has the ability to significantly…
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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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Finding unique drug structures with artificial intelligence and chemistry
In the search for new medicines against diseases such as cancer, a Leiden team has developed a new workflow. This approach combines artificial intelligence (AI) with molecular modelling and is suitable for finding unknown and innovative drug structures, the researchers proved.
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Chemical tools to monitor and control human proteasome activities
Promotores: H.S. Overkleeft; G.A. van der Marel Co-Promotor: B.I. Florea
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Tom van der Wel
Science
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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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Mario van der Stelt
Science
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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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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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Jeroen Codee
Science
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Calcium-dependent regulation of auxin transport in plant development
The plant hormone auxin regulates plant growth and development through polar cell-to-cell transport-generated maxima and minima. PIN FORMED (PIN) auxin efflux carriers determine the direction of this auxin flow through their asymmetric placement on the plasma membrane (PM).
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Molecular Physiology
Molecular Physiology is a research group at the Leiden Institute of Chemistry dedicated to the design, synthesis and application of chemical tools to study important biological and biomedical questions. The group is headed by Prof. Dr. Mario van der Stelt and includes the research lines of Assistant…
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Activity-based protein profiling for drug discovery
Activity-based protein profiling (ABPP, also termed chemical proteomics), is one of the pillars of chemical biology, and at LED3 we have taken it to the next level. ABPP allows the assessment of protein function in live cells and tissues, which means that the activity of a complete protein family can…
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Polar auxin transport: translating environmental signals into plant developmental responses
1. What is the exact role of PIN proteins in PAT? 2. How is PIN polarity established, and how is it modulated by AGC kinase-mediated phosphorylation? 3. What is the role of the AGC kinase, as modulators of PAT, in translating environmental signals, such as gravity, light or mechanical stress, to plant…
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In Memoriam Professor Huib Ovaa
On the 19th of May 2020, our dear colleague and friend Professor Dr. Huib Ovaa has passed away from prostate cancer. Last summer Huib became ill, and in first instance it appeared that he had attracted a relatively harmless infectious disease. Unfortunately, it became soon apparent that he suffered…
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Microbial Chemotaxis
In order to gain insight into the structure and function of the molecular complexes involved in chemotaxis, we use electron cryotomography (ECT). This technique allows us to directly study microbes in their native state at resolutions capable of visualizing individual proteins.
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Elmer Maurits
Science
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Hermen Overkleeft
Science
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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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Key publications
Key publications of the Cancer Drug Target Discovery group
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Immune checkpoint inhibitors in mesothelioma
PhD defence
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New technique offers chemists unprecedented control in drug research
Leiden chemists have developed a new technique with which they can determine the role of kinases – a group of proteins – in a living cell. This technique makes it easier to find new drug targets for diseases such as cancer and rheumatoid arthritis. The team published the findings in the journal Nature…
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EGFR inhibitors in colorectal cancer
PhD defence
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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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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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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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Indanes-Properties, Preparation, and Presence in Ligands for G Protein Coupled Receptors
The indane (2,3-dihydro-1H-indene) ring system is an attractive scaffold for biologically active compounds due to the combination of aromatic and aliphatic properties fused together in one rigid system.
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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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Flagships
In CCLS several subgroups have formed, below you can find an overview of these groups with the names of the leading researchers and a short outline of the project.
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Proteochemometric modelling coupled to in silico target prediction
An integrated approach for the simultaneous prediction of polypharmacology and binding affinity/potency of small molecules.
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Proteins in harmony: Tuning selectivity in early drug discovery
This thesis describes the importance of being able to control the selectivity of potential drug candidates.
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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.
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Cheminformatics: Analyzing small-molecule activity data
While bioinformatics methods deal with the analysis of sequence information (be it proteins or DNA), the field of cheminformatics is concerned with the analysis of small-molecule datasets.
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Understanding functional dynamics and conformational stability of beta-glycosidases
Due to their central physiological roles in living organisms, retaining beta-glycosidases have been the subject of tremendous research efforts to examine their structure/function relation using numerous biophysical and biochemical approaches.
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LACDR excels at the FIGON Dutch Medicine Days
The Leiden Academic Centre for Drug Research (LACDR) received no less than three awards during the Figon Dutch Medicine Days. Bas Goulooze won the PhD Prize for best PhD candidate, Natalia Ortiz Zacarías and Huub Sijben both received a poster prize. ‘Scientists must be able to communicate their research…
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LIC Lecture: Structure-based development of immunoproteasome inhibitors
Lecture
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Research
Research at the BIOSYN group is comprised of the following research themes:
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Fundamental Research in Chemical Biology
Chemical biology research at the Leiden Institute of Chemistry is aimed at understanding biological processes at the molecular level to strengthen the knowledge base of human health and disease. The approach to achieve this goal is a fundamental chemical one; with the aid of chemical probes biological…
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Proteochemometrics
Research question
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Chemical tools to modulate endocannabinoid biosynthesis
Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt
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Projects
Research projects
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Synthesis of chemical tools to study the immune system
This thesis describes the synthesis and biological evaluation of TLR2/6, TLR4, TLR7/8 and TLR9 ligands, of which the activity can be conditionally controlled.
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NO-ESKAPE New Strategies for Overcoming the ESKAPE Pathogens
Natural product inspired antibiotics to address resistance
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Chemical Tools to Illuminate N-acylphosphatidylethanolamine Biosynthesis
This thesis describes the development and optimization of the first molecular tools to study the enzyme PLA2G4E.
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Medical Biochemistry
Medical Biochemistry is a section of the Leiden Institute of Chemistry at Leiden University. The section is headed by Prof. Dr. Hans Aerts.
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Protein Facility
The Protein Centre can supply you with purified proteins that are essential for many experiments, ranging from in vitro inhibitor screening and enzymatic analysis to manipulation of life cells.
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PI3K signaling and adherens junctions in invasive lobular breast cancer
Invasive lobular carcinoma (ILC) is the second most common type of breast cancer.