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

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.

Science, Leiden Academic Centre for Drug Research (LACDR)

In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based…

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…

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

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

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.

High-throughput holistic preclinical screens are increasingly used in drug discovery, to assess both drug efficacy and drug safety.

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 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.

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…

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

Discovery of metastasis promoting candidate drug targets

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.

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.

Professor of Clinical Pharmacology Adam Cohen from Leiden University received the prestigious Dr. Saal van Zwanenberg Honorary Prize on 12 November. The prize honours a scientist who has distinguished themselves in the field of research that has directly or indirectly led to the development of new medicines…

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

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…

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

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.

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

Pharmaceutical companies, governments and the general public have become increasingly aware that animal models used in drug testing lack vital aspects to serve as an accurate representation of human biology. As models of the human body should become more physiologically relevant, animal models no longer…

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

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.

During the course of drug discovery translational steps are made.

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…

Source: ChemMedChem (2015)

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.

Fascinated by science since high school, Alireza Mashaghi Tabari is driven to explore new ways of thinking in medicine. With a strong academic network, he educates students and gives public lectures. For his research at LACDR, he won the C.J. Kok Public Award 2018, making him the Faculty of Science's…

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. Kros

PhD defence

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

A main goal of MSBB research is to address the major bottle-necks in combatting viral diseases: the lack of experimental models that are representative of human pathology and are cost effective and versatile. Viral diseases such as those that cause viral hemorrhagic syndromes or severe acute respiratory…

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

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

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

Accurate prediction of the unbound drug concentration-time profile at the CNS target site is crucial for the assessment of the right drug concentration-effect relationship. PBPK models have supported the PK prediction of the CNS target sites and the translation of PK data between species and between…

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

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.

In the Phenomix Medical Delta Field Lab, which was officially opened on Thursday 9 July, scientists, healthcare institutions and businesses work together to develop innovative applications in the field of metabolomics. This research field makes it possible to determine which drugs will be effective…

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

Analysis of drug adversity

The zebrafish is a promising vertebrate model organism in early drug discovery and development.

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…

Cancer is one of the main causes of death in the Netherlands. Leiden researchers are working to improve the treatment of different types of cancer in order to increase the patient’s quality of life. A better understanding of how cancer develops will make it possible to deliver personalised and precise…

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