A next, general pharmacological problem to be tackled is how drug-target binding kinetics in vivo, affects target occupancy as an important indicator of the time-course of drug effects.

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.

Harm reduction in practice: a comparative analysis of the Dutch and Brazilian approach towards drug users.

Discovery of metastasis promoting candidate drug targets

Science, Leiden Academic Centre for Drug Research (LACDR)

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As leading cause of death worldwide, cancer is responsible for nearly 10 million deaths in 2020 according to World Health Organization (WHO). Cisplatin and its derivatives are commonly used chemotherapy agents for current cancer treatment in the clinics.

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…

Benjamin Fogarty-Valenzuela published the article 'Pedagogies of Prohibition: Time, Education, and the War on Drugs in Rio de Janeiro’s Zona Norte' in Cultural Anthropology 37. The article’s three sections focus on three forms of temporal control—busyness, punctuality, and rhythm—and each demonstrates…

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.

Can we develop a generic method for Quan/Qual analysis of small molecule drugs, their metabolites and endogenous metabolites in (pre-)clinical samples?

Although rarely considered by the pharmaceutical industry or clinicians, 24-hour rhythms in physiology are a factor of potential influence on the pharmacokinetics and pharmacodynamics of drugs.

Another research line is the development of a spatial CNS drug distribution model, by ultimately including the 3-dimensional anatomical organization of the CNS.

How can we extend the drug residence time to combat diseases more effectively?

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

During the course of drug discovery translational steps are made.

How can zebrafish research help to understand and fight human cancer?

Source: ChemMedChem (2015)

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

Can effective synergists be identified to enhance the effect of antibiotics against Gram negative pathogens?

Data analysis with Python and R are rapidly becoming essential skills for modern scientists. Therefore, we are offering courses to develop your scientific computing skills. Those courses are optional for LACDR PhD candidates.

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Human and animal cells are very complex: very different chemical processes are going on at the same time, but they are separated from each other because the cells are divided in compartments. These compartments may also have a profound effect on the potential efficacy of therapeutics, because the drug…

The GMP Facility facilitates development and production of Advanced Therapy Medicinal Products (ATMPs) and chemical (peptide) synthesis.

Promotor: A. Kros

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…

Promotores: Prof.dr. H. S. Overkleeft, Prof.dr. G. A. van der Marel

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

This project’s aim is to critically assess current homicide data sources in order to develop a proposal for long-term EU-level monitoring of DRH.

Exploring the mechanism of targeted nanoparticle-mediated drug delivery using the zebrafish model

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

The lack of success of new CNS drugs in clinical development is in part due to the complexity of the CNS, unexpected side effects, difficulties for drugs to penetrate the brain, but also by the lack of biomarkers.

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

Analysis of drug adversity

Establishing human induced pluripotent stem cell (iPSC) CRISPR-Cas9-based fluorescent reporter cell lines for NF-kB signalling. We will use this to enable studying the dynamic activation and downstream signalling of Toll-like receptor and cytokine signalling in iPSC-derived differentiated cells in a…

The path to rational drug and dose selection

Source: Nature Biotechnology, Volume 2014, Issue June (2014)

From descriptive to physiological models that can predict oral absorption and elimination of CYP3A substrates across the pediatric age range.

High throughput microscopy

He’s a fast and animated speaker, which is only logical because Gerard van Westen is driving an express train. His destination? A virtual human, consisting of algorithms that predict what an administered substance will do in the body. The train is already a long way down the line and the pharmaceutical…

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