How are new drugs developed? This question is central to the Minor Modern Drug Discovery (MDD), which covers the entire trajectory from disease to drug molecule and vice versa. The various research groups involved offer a complementary and interdisciplinary perspective by connecting the diverse subjects…

In het onderzoeksprogramma Drug Discovery & Safety zijn we geïnteresseerd in de werkzaamheid en veiligheid van nieuwe medicijnen en nieuwe manieren om deze aspecten te bepalen. Daarvoor combineren we geavanceerde imaging en high-throughput screening technieken met computationele aanpakken zoals chem-…

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.

O-Nitrobenzyl groepen worden veel gebruikt als moleculaire beschermgroepen die je met licht kunt verwijderen.

Hospital pharmacies face significant challenges: the demand for sterile drug reconstitutions is increasing, while specialized personnel remain scarce. Automation offers a potential solution, but its practical implementation in hospitals is still unclear.

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

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

Glucocorticoids are potent anti-inflammatory drugs widely used clinically to treat various inflammatory and immune conditions. However, two main clinical problems limit their use. GCs trigger severe side effects and they induce acquired glucocorticoid resistance, especially during chronic systemic treatment…

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…

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.

Promotor: M. Danhof Co-promotor: O.E. Della Pasqua

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

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

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.

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.

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

During the course of drug discovery translational steps are made.

This thesis investigates how non-genetic factors, such as inflammation and concomitant medication, impact hepatic drug metabolism and subsequent drug metabolizing phenotype predictions.

Promotor: A. Kros

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

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: R.G. Boot

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.

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

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

Promotor: A.P.IJzerman Co-promotor: A. Bender

Promotor: B. van de Water

Growth hormone profiles are pulsatile and highly variable between individuals, limiting the implementation of mathemathical models to quantify an individual's secretion.

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

Model based approaches, integrating physiological parameters or linking exposure with response, are powerful tools to quantify and evaluate the impact of genetic differences that are reflected as variability of drug exposure and/or clinical response(s). This thesis “Pharmacogenomics in Drug Development: …

The path to rational drug and dose selection

Een pilletje op een festival, een biertje in de kroeg, of een sigaret bij de koffie. We wéten dat het slecht voor ons is, maar doen het toch. Hoe komt dat?

The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.

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

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.

This thesis focuses on data found in the field of computational drug discovery. New insight can be obtained by applying machine learning in various ways and in a variety of domains. Two studies delved into the application of proteochemometrics (PCM), a machine learning technique that can be used to…

In dit artikel herzien Marieke Liem en Kim Moeller Goldstein’s kader over het verband tussen drugs en geweld.

Microscopic insight on lipid-based nanomedicine in vivo remains limited to the perception of the knowledge that could be obtained: if we interpret only what we see, then we only believe to know. Although believing to know encapsulates an undefined amount of uncertainty in the exploration of lipid-based…

With an emphasis on developing novel miktoarm star polymers termed PeptoMiktoStars, this thesis leverages asymmetric polymeric polypept(o)ide frameworks to advance their effectiveness in delivering hydrophobic drugs and nucleic acids.

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…

Het Antoni van Leeuwenhoek/Nederlands Kanker Instituut, het Leids Instituut voor de Chemie en het Pivot Park Screening Centre gaan kennis en infrastructuur delen in het Cancer Drug Discovery Initiative. Vrijdag 11 oktober tekenden ze een letter of intent.

Utilizing the polymeric platform of polypept(o)ides, this thesis describes synthesis and investigation of novel triblock copolymers to obtain carrier systems with multiple compartments for efficient siRNA delivery. Although the individual microstructure of nanoparticles differs depending on the polymeric…

Heeft het gebruik van medicijnen en drugs invloed op mijn persoonlijkheid? Wat zijn de (langere-termijn) gevolgen van de leerpil 'Ritalin'? Kunnen (party)drugs en medicijnen met rijden in het verkeer samengaan? Wat doen verslavende stoffen met mijn brein?

Met ingang van 1 april 2018 is Erik Danen benoemd tot hoogleraar Cancer drug target discovery bij het Leiden Academic Centre for Drug Research (LACDR). Zijn vakgebied is celbiologie van kanker, waarin hij zich richt op de achterliggende mechanismen bij uitzaaiingen en resistentie voor behandelingen.

The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

Stimulerende drugs als khat en cocaïne hebben negatieve impact op dagelijkse handelingen als autorijden, werk of sociaal gedrag. Dat komt door beschadiging van controlefuncties in de hersenen. Psycholoog Manuel Ruiz draagt bij aan beter begrip en behandeling van drugsmisbruik. De Spanjaard Ruiz promoveert…

M. Danhof, Co-promotores: J. Freijer, A. Yassen

This thesis focuses on enhancing predictions of central nervous system drug exposure using the LeiCNS-PK3.0, a physiologically based pharmacokinetic model.