Glucocorticoids are potent anti-inflammatory drugs widely used clinically to treat various inflammatory and immune conditions. However, two main clinical problems limit their use. GCs trigger severe side effects and they induce acquired glucocorticoid resistance, especially during chronic systemic treatment…

Cardiovascular diseases are among the most frequent causes of death in the world. The main underlying pathology of cardiovascular diseases is the development of atherosclerosis in the medium and large-sized arteries.

Glucocorticoids (GCs) are widely prescribed as anti-inflammatory drugs due to their well-established immunosuppressive effects.

O-Nitrobenzyl groepen worden veel gebruikt als moleculaire beschermgroepen die je met licht kunt verwijderen.

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…

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

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.

Promotor: M. Danhof Co-promotor: O.E. Della Pasqua

Wiskunde en Natuurwetenschappen, Leiden Academic Centre for Drug Research (LACDR)

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-…

Hospital pharmacies face significant challenges: the demand for sterile drug reconstitutions is increasing, while specialized personnel remain scarce. Automation offers a potential solution, but its practical implementation in hospitals is still unclear.

A novel mathematical model describes spatial-temporal drug distribution within one or more brain units, which are cubic representations of a piece of brain tissue with brain capillaries at the edges.

Promotor: B.van de Water, Co-promotor: L.S.Price

Endothelial dysfunction and microvascular diseases are key drivers of cardiovascular disease, the world's leading cause of death.

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.

Over several decades, a variety of computational methods for drug discovery have been proposed and applied in practice. With the accumulation of data and the development of machine learning methods, computational drug design methods have gradually shifted to a new paradigm, i.e. deep learning methods…

This thesis focuses on the role of chemokine receptors CXCR3 and CCR2 in the inflammatory process and infection control using the zebrafish model.

Promotor: Prof.dr. M. Danhof, Co-Promotor: J. de Jongh

The Minor Computational Approaches to Disease, Signaling and Drug Targets (CADSDT) is focused on fundamental scientific research required for discovery of new drug targets and development of new drugs.

This thesis focuses on the application of lipid-based nanomedicine in drug delivery, including small molecular antitumor drugs and biomacromolecules including mRNA, and evaluates their biological performance.

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

This thesis investigates how non-genetic factors, such as inflammation and concomitant medication, impact hepatic drug metabolism and subsequent drug metabolizing phenotype predictions.

During the course of drug discovery translational steps are made.

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

Promotor: A. Kros

M van der Stelt

Promotor: Prof.dr. J. Kuiper

Een pilletje op een festival, een biertje in de kroeg, of een sigaret bij de koffie. We wéten dat het slecht voor ons is, maar doen het toch. Hoe komt dat?

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: R.G. Boot

Microglia support the central and peripheral nervous system by forming the first line of defense against hazardous events. Microglia are increasingly acknowledged as critical players in neurodegenerative diseases, highlighting them as potential therapeutic targets.

Acute cardiovascular syndromes, including myocardial infarction or stroke, are the principal cause of death in the Western society. The main underlying pathology of cardiovascular diseases is atherosclerosis, which is caused by the accumulation of lipids and inflammatory cells in the vessel wall, in…

Clinical development of drugs for central nervous system (CNS) disorders has been particularly challenging and still suffers from high attrition rates.

Promotor: A.P. IJzerman Co-promotor: L.H. Heitman

Discovery and development of Central Nervous System (CNS) drugs is hampered by high attrition rates.

The aim of this thesis is to expedite and ensure the systematic accuracy of clearance scaling from adults to paediatric patients, with a special focus on drugs undergoing hepatic metabolism.

Promotor: A.P.IJzerman, Co-Promotor: L.H. Heitman

Model based approaches, integrating physiological parameters or linking exposure with response, are powerful tools to quantify and evaluate the impact of genetic differences that are reflected as variability of drug exposure and/or clinical response(s). This thesis “Pharmacogenomics in Drug Development: …

In dit artikel herzien Marieke Liem en Kim Moeller Goldstein’s kader over het verband tussen drugs en geweld.

The path to rational drug and dose selection

Promotores: C.A.J. Knibbe; J.N. van den Anker, Co-promotores: H.P.A. van Dongen; B. van Ramshorst

Promotor: A.P.IJzerman Co-promotor: A. Bender

Promotie

Growth hormone profiles are pulsatile and highly variable between individuals, limiting the implementation of mathemathical models to quantify an individual's secretion.

Promotor: B. van de Water

This thesis investigates a pharmacological challenge model induced by Toll-like receptor 7 (TLR7) activation, focusing on skin inflammation and its implications for early drug development.

Drug induced organ toxicity is the main problem of the drug development and drug usage in the clinic. The liver and kidneys are the most sensitive organs towards drug induced toxicity.

Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)

With an emphasis on developing novel miktoarm star polymers termed PeptoMiktoStars, this thesis leverages asymmetric polymeric polypept(o)ide frameworks to advance their effectiveness in delivering hydrophobic drugs and nucleic acids.

The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.

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…