Universiteit Leiden

Two department of the University of Leiden are involved in the K4DD project:

The Department of Medicinal Chemistry
The Department of Medicinal Chemistry within the Leiden Academic Centre for Drug Research of the University of Leiden combines:

  1. designing and synthesizing novel ligands (organic chemistry)
  2. making mutant receptors (molecular biology)
  3. characterizing novel ligands (molecular pharmacology)
  4. making receptor/ligand models (bio/cheminformatics) to get a better understanding of a drug-receptor interaction and, thereby, making better drug candidates.

We have chosen the most important class of drug targets to work on, the G protein-coupled receptors (GPCRs). Close to half of all medicines work via these targets in our body. As there are over 800 of them in the human body, we have selected a few to concentrate on; receptors for adenosine, for gonadotropin-release hormone, for chemokines and for nicotinic acid.Moreover, we focus on so-called receptor concepts rather than a particular disease area, which include allosteric modulation, biased signaling, inverse agonism/constitutive activity and receptor residence time.

The Division of Pharmacology
The division of pharmacology focuses on the analysis of in vivo and clinical pharmacokinetic and pharmacodynamic studies. A computational approach is used to generate pharmacokinetic-pharmacodynamic [PK-PD] models based on experimental data. Our research in PK-PD modeling focuses on mechanism-based models with excellent extrapolation and prediction properties. A key element is the explicit distinction between parameters for describing drug-specific and biological system-specific properties as determinants of the pharmacological response. Mechanism-based PK-PD models contain specific expressions for describing processes on the causal path between drug exposure and drug response. The different terms represent: target site distribution, target binding/activation, and transduction. Ultimately, mechanism-based PK-PD models will also describe the interaction with disease processes and disease progression. In increasing order of complexity our research focuses on the development of novel concepts of PK-PD modeling in: i] translational pharmacology [the prediction of efficacy- safety from preclinical tests], ii] developmental pharmacology [the prediction of variability in drug response in pediatrics], and iii] disease systems analysis [the prediction of drug effects on disease progression].