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.

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.

The spindle-assembly checkpoint (SAC) is a safety mechanism which secures accurate chromosome segregation during mitosis.

Diacylglycerol lipases (DAGLα and DAGLβ) are responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain and peripheral tissues. Selective DAGLβ inhibitors have been proposed as a potential treatment for inflammatory diseases with reduced potential for central…

Promotor: G.P. van Wezel, Co-promotor: Y.H. Choi

Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.

Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt

Antibioticaresistentie is een van de grootste bedreigingen wereldwijd voor de volksgezondheid in de komende decennia.

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.

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.

How are new drugs developed? This question is central to the Minor Modern Drug Discovery (MDD), which covers the entire trajectory from disease to drug molecule and vice versa. The various research groups involved offer a complementary and interdisciplinary perspective by connecting the diverse subjects…

Pectin is a plant cell wall polysaccharide made of mainly D-galacturonic acid (GA) subunits. The potency of the filamentous fungus Aspergillus niger to naturally secrete high amounts of pectinases to degrade pectin has been utilized for the industrial production of pectinases.

In het onderzoeksprogramma Drug Discovery & Safety zijn we geïnteresseerd in de werkzaamheid en veiligheid van nieuwe medicijnen en nieuwe manieren om deze aspecten te bepalen. Daarvoor combineren we geavanceerde imaging en high-throughput screening technieken met computationele aanpakken zoals chem-…

The main aim of this project is to reveal and unravel the invisible histories of the UN, transcending the dominant Western perspective to recover the historical agency of Global South actors. The research will investigate how the UN has both facilitated and limited their role in shaping global order…

Heart failure is a major health care problem with high mortality.

The adenosine receptors are proteins that reside in the extracellular membranes of cells. Activation of adenosine receptors plays a role in many physiological and pathological processes, such as immune responses and cancers.

Drug-target binding kinetics determine the time course of the central event in pharmacotherapy: Drug-target interaction.

Promotor: Prof.dr. T. Hankemeier, Prof.dr. J.C.T. Eijkel (Twente University)

The aim of this thesis was to develop novel treatment strategies for different types of eye melanoma utilizing zebrafish models. We first establish orthotopic and ectopic xenograft models for uveal and conjunctival melanoma by engraftment of the immortalized cells derived from these tumors into zebrafish…

Within this thesis the central stage is taken by the discovery and investigation of transglycosylation of sterols. First, investigation focuses on the development of a method to accurately detect and quantify glucosylated metabolites in biological materials.

This thesis describes the importance of being able to control the selectivity of potential drug candidates.

Plastics are an intrinsic part of our society. Annually, 400Mt of plastics are produced of which roughly 40% is discarded within a year.

In the emerging field of small-molecule RNA targeting, there is a growing demand for new high-throughput screening methods.

Promotor: Prof.dr. R. Verpoorte, Co-Promotor: Dr. Young Hae Choi

This thesis focuses on data found in the field of computational drug discovery. New insight can be obtained by applying machine learning in various ways and in a variety of domains. Two studies delved into the application of proteochemometrics (PCM), a machine learning technique that can be used to…

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.

Cancer is considered the silent pandemic of the 21st century and the second leading cause of death worldwide.

Promotor: A.P. IJzerman

De tweejarige masteropleiding Philosophy of the Arts van de Universiteit Leiden biedt de mogelijkheid om je te specialiseren in conceptuele en methodologische kwesties in de geesteswetenschappen.

Subproject of the ERC project 'Challenging the Liberal World Order from Within: The Invisible History of the United Nations and the Global South'.

Metastasis is responsible for over 90% of cancer-related deaths and arises from the ability of a small subset of tumor cells to detach from the primary tumor, overcome multiple biochemical and mechanical barriers, disseminate through the body, and colonize distant organs.

This minor is focused on fundamental scientific research required for discovery of new drug targets and development of new drugs. Students learn how disease and drug-induced alterations in signaling pathways can be used for the discovery of new drug targets and the development of personalized drugs.

Subproject of the ERC project 'Challenging the Liberal World Order from Within: The Invisible History of the United Nations and the Global South'.

Het Antoni van Leeuwenhoek/Nederlands Kanker Instituut, het Leids Instituut voor de Chemie en het Pivot Park Screening Centre gaan kennis en infrastructuur delen in het Cancer Drug Discovery Initiative. Vrijdag 11 oktober tekenden ze een letter of intent.

The energy system is at the heart of two of the greatest challenges of the 21st century: decreasing CO2 emissions to meet the ambitions of the Paris agreement while fulfilling the growing energy demand associated with the economic aspirations of a growing world population.

Filamentous Actinobacteria, such as Streptomyces, produce a plethora of chemically diverse bioactive metabolites that have found applications across medicine, agriculture and biotechnology.

According to the amyloid cascade hypothesis, accumulation of beta-amyloid (Aβ) peptides initiates the pathological cascade in Alzheimer's disease (AD).

This thesis describes the design and development of subunit‐selective inhibitors of particular catalytically active subunits of human constitutive proteasomes and immunoproteasomes.

Promotor: T. Hankemeier, Co-promotor: R.J. Vreeken