An integrated approach of physiological concepts, advanced statistical approaches and large clinical datasets.

The path to rational drug and dose selection

The kidneys play a major role in the elimination of drugs. In children, the exact age-related physiological changes underlying kidney function remain largely unknown.

Prof. Elizabeth de Lange is concerned with the allocation of resources for the conduct of science towards the goal of best serving the public interest. Also, while she underscores that there is still the need for using animals in drug research, she is concerned about this use, and advocates the use…

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.

Timely, adequate and optimal treatment of infectious diseases is essential for the survival of patients with bacterial infections (Surviving Sepsis campaign).

The aim of this research area is to be able to predict human drug response on the basis of mathematical models that are developed using preclinical experiments and prior knowledge.

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

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

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

Drug development is a complex process in which many parties work together. Every day, the researchers at LACDR devote their energies to developing drugs that are new, better, more efficient and easier to produce. And thus to the millions of patients who know all too well why this research in Leiden…

Is is possible to better predict the validity of drug candidates?

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…

In the future, physicians may be able to identify dementia much earlier than they can today because a computer algorithm will be able to predict from brain scans how our memory is going to develop.

Promotores: Prof.dr. W.J.G.M. Peijnenburg & Dr. M.G. Vijver

How to make a quantitative assessment of the relative contribution to toxicity of ions and particles? Is the toxicity of nanoparticles related to their size or shape? Which physicochemical property of nanoparticles is an appropriate dose metric of nanoparticles?

Clearance is the most important pharmacokinetic parameter for drug dose selection. Pharmacokinetic information is typically first available in the adult population, and in general only limited pharmacokinetic data are available in children when drugs enter into the market. It is therefore of the utmost…

In this thesis population pharmacokinetic and physiologically-based pharmacokinetic (PBPK) approaches were applied to investigate the influence of glomerular filtration (GF) and active tubular secretion (ATS) on renal clearance in children.

Drug-related homicide (DRH) has the potential to act as a valuable indicator of wider drug-related crime. Yet DRH remains a knowledge gap within this broader field of study.

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.

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

Less than 1 in 10 drug candidates that enter phase 1 clinical trials actually gets approved for human use.

Supervisor: Gerard van Westen

Our research in the area of safety sciences aims to increase the mechanistic understanding of cellular toxicity of drugs and, in a broader sense, chemicals.

Promotor: C.A.J. Knibbe, Co-promotores: H.P.A. van Dongen, B. van Ramshorst

Research in this group, headed by Gerard van Westen, focusses on computational methods integrated in different parts of the drug discovery process. More specifically, topics include innovative treatments for cancer, selectivity modeling, translational research, allosteric modulation, drug resistance…

In the theme Drug research we generally work with rodents.

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

There are many complex links in the chain that provides patients with new drugs: from fundamental science, to clinical tests, to production. The entire chain can be found in Leiden. Leiden University, the Leiden University Medical Center (LUMC) and the businesses at the Leiden Bio Science Park (LBSP)…

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

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

An integrated approach for the simultaneous prediction of polypharmacology and binding affinity/potency of small molecules.

Can drugs that target host signaling pathways be used to eradicate antibiotic-resistant bacteria?

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.

Source: Nat Biotechnol, Volume 32, Issue 12, pp. 1213-22 (2014)

To get a feeling of how we operate at LED3 when it comes to Early Drug Discovery, please browse through our case studies. When you select a case study you’ll find relevant contacts.

Promotor: C.A.J. Knibbe, Co-promotor: J.J. Boelens, R.G.M. Bredius

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 this research group, headed by Bob Van de Water, cell signaling programs that underlie adverse drug reactions as well as cancer development and progression are unraveled. Adverse drug reactions involve cell injury in critical target organ cells which leads to the activation of cellular stress response…

In the research programme Drug Discovery & Safety, we are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

The drug discovery pipeline is used to describe the stages in drug discovery. The earliest stage concerns with the identification of potential targets and molecules ('hits') that can modulate their function, while more advanced stages are about developing these hits into viable experimental drugs and…

The Data-Driven Drug Discovery Network (D4N) is an initiative by researchers from Leiden University and collaborators to join efforts in applying and developing novel techniques from data science to drug discovery and related topics from bioinformatics.

The field of exoplanet research is rapidly advancing through the development of new technology, observing techniques, and post-processing methods.

We focus on a better understanding of the mechanisms of cancer drug resistance and metastasis.

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

In this research group, headed by Prof. Erik Danen, the aim is to unravel cellular signaling mechanisms in normal and diseased cells, with a long-standing interest in cell adhesion signaling. In complex multicellular organisms such as ourselves, a division of labor emerges where different tissues and…

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

Promotores: Prof.dr. M. Danhof, Prof.dr. D.R. Stanski

Science, Leiden Academic Centre for Drug Research (LACDR)