A tantalizing concept that has emerged in our recent research is binding kinetics. An important parameter is residence time (RT), a direct reflection of how long a drug stays bound to its target. This parameter is of crucial importance, because drug action lasts only as long as the receptor-ligand complex…

Supervisor: Gerard van Westen

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.

Source: ChemMedChem (2015)

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

The present thesis focuses on the pharmacological concept of drug-target interaction, which dates back to the beginning of modern pharmacology.

During the course of drug discovery translational steps are made.

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

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

Source: Br. J. Pharmacol., Volume 172, Issue 3, pp. 940-55 (2015)

Supervisor: Anna Vlachodimou

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

Supervisor: Lizi Xia

Structure-affinity relationship (SAR) and structure-kinetics relationship (SKR) studies were combined to investigate a series of biphenyl anthranilic acid agonists for the HCA2 receptor.

Source: Eur J Med Chem, Volume 101, pp. 681-91 (2015)

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

Supervisor: Andrea Martella

The Cide Archaeological Project: Surveying the Turkish Western Black Sea Region

Supervisor: Maarten Doornbos

Source: J Med Chem (2015)

Potential drugs that seem promising in the lab, but don’t show any activity in a person: they cost the industry an incredible amount of time and money. That’s why Indira Nederpelt focuses on a more efficient search for new drugs in her PhD, by determining the kinetics of a potential drug earlier on…

Supervisor: Indira Nederpelt

Adenosine is an endogenous ligand which exerts its action by activating adenosine receptors (ARs), while its circulating levels are controlled via a variety of mechanism and proteins, amongst others the equilibrative nucleoside transporters (ENTs).

Although it is often assumed that the stereochemistry in Ugi multicomponent reactions is determined in the final Mumm rearrangement step, experimental and computational evidence that Ugi reactions on hydroxylated pyrrolines proceed under kinetic control is reported.

Source: J Med Chem, Volume 57, Issue 8, pp. 3213-22 (2014)

This Thesis shows discoveries in non-linear astrochemical kinetics as well as a deeper analysis of dark clouds chemistry.

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

A difficulty of studies on chemical kinetics are the reaction time scales and detection of their intermediates.

In this research group, headed by Laura Heitman, novel receptor concepts in drug discovery are studied, aiming to increase the effectivity of medicines. Many drugs act via so-called G protein-coupled receptors (GPCRs) and therefore our research is mainly focused on understanding and improving drug-receptor…

Supervisor: Gerard van Westen

An overview of research projects at the Predictive Pharmacology group.

The receptor nomenclature committee of IUPHAR, the International Union of Pharmacology, has several subgroups. Among these are a few that our division is involved in, those for adenosine, nicotinic acid, and GnRH receptors.

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.

Source: Mol Pharmacol, Volume 87, Issue 2, pp. 305-13 (2015)

Source: Eur J Med Chem (2015)

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.

Not taking into account the saturation of drug targets can lead to wrong conclusions about the duration of a drug's action. This is what former PhD candidate Wilbert de Witte writes together with the Leiden professors of pharmacology Meindert Danhof, Piet van der Graaf, and Liesbeth de Lange in Nature…

Designing and synthesizing high-affinity ligands for a given drug target have always been among the more important challenges in the drug discovery process.

PhD defence

The mission in this research group, headed by Ad IJzerman, is to design and synthesize novel and better ligands for drug targets. Drug discovery is a lengthy but inspiring adventure. It is often an interplay between academic institutes and pharmaceutical industry, in which scientists at university develop…

Research question

The studies presented in the work show the potential of the integrative use of biophysical data in defining the structural basis of protein interactions.

It is estimated that approximately 30% of all proteins require a metal to function. Investigating the relationship between metal-binding and peptide/protein folding allows us to uncover fundamental rules for creating metallo-peptides and proteins, which in turn leads to the creation of new structures,…

Detection of cerebral beta-amyloid (Abeta) by targeted contrast agents remains of great interest to aid the in vivo diagnosis of Alzheimer's disease (AD). Bis-styrylbenzenes have been previously reported as potential Abeta imaging agents.

Laura Heitman of the Leiden Academic Center for Drug Research (LACDR) has been nominated for the Prix Galien Research Award. This important pharmaceutical prize honors young, prominent researchers whose scientific research is of great importance for fundamental or clinical drug research.

Together with Pepijn Tuinier and Thijs Brocades Zaalberg, Sebastiaan Rietjens researched the role of trust in an international intelligence cooperation.

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.