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.

Promotores: W. Jiskoot, F. Ossendorp

Het ontwikkelen van nieuwe medicijnen is een complex proces waarbij veel partijen samenwerken. De onderzoekers van het LACDR zetten zich dagelijks in voor nieuwe, betere, efficiëntere en makkelijker produceerbare medicijnen. Het instituut werkt nauw samen met het LUMC, met bedrijven op het Leiden Bio-Science…

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.

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…

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.

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

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.

Promotie

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

Promotie

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…

During the course of drug discovery translational steps are made.

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

Promotie

Promotor: A. Kros

M van der Stelt

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

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

Promotor: H.S. Overkleeft, J. Neefjes, Co-promotor: M. van der Stelt

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

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.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection, it is associated with significant morbidity, mortality, and with a high financial burden on global healthcare systems. Bacterial infections are the primary cause of sepsis, but the growing prevalence of antimicrobial…

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

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

The research presented in this thesis explores the chemotherapeutic potential of metal-based compounds as chemotherapy agents, with an initial focus on the synthesis and DNA interaction studies of platinum and palladium compounds utilizing the [Pt(bapbpy)]2+ scaffold. The study identifies intercalation…

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

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

In order to be able to develop effective medicine and treatments to prevent or cure autoimmune diseases or cancer we need to understand the mechanisms how they arise and what drives their course.Unravelling the fundamental molecular mechanisms influencing the onset and course of diseases such as allergies,…

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.

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.

Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern.

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.

This thesis represents a comprehensive investigation into the control of cancer stemness and metastatic initiation using a combination of advanced zebrafish xenograft models and in vitro assays.

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

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.

The aim of this thesis was to develop novel treatment strategies for different types of eye melanoma utilizing zebrafish models. We first establish orthotopic and ectopic xenograft models for uveal and conjunctival melanoma by engraftment of the immortalized cells derived from these tumors into zebrafish…

As leading cause of death worldwide, cancer is responsible for nearly 10 million deaths in 2020 according to World Health Organization (WHO). Cisplatin and its derivatives are commonly used chemotherapy agents for current cancer treatment in the clinics.

Promotor: Prof.dr. R. Verpoorte, Co-Promotor: Dr. Young Hae Choi

Death in all types of melanomas is generally caused by metastasis. Uveal melanoma (UM) is the most common intraocular melanoma, there are currently no (patient-derived) animal models that faithfully recapitulate metastatic dissemination of UM.

Promotie

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…

Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.

Promotores: Prof.dr. P.C.W. Hogendoorn & Prof.dr. H.P. Spaink Co-promotor: Dr. B.E. Snaar-Jagalska

The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.

The soil-dwelling, filamentous bacteria of the genus Streptomyces are renowned for their production of useful secondary metabolites including antibiotics. The work described in this thesis provides new insights on the role and regulation of antibiotic production and resistance in these bacteria.

Glucocorticoids (GCs) are widely prescribed as anti-inflammatory drugs due to their well-established immunosuppressive effects.