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Frederik Pruijn

Frederik Pruijn

Frederik Pruijn obtained his PhD in Pharmacochemistry at the Vrije Universiteit in Amsterdam. Since 1992 he has been affiliated with the University of Auckland, New Zealand, and is a Senior Research Fellow in the Auckland Cancer Society Research Centre.
 

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Frederik Pruijn obtained his training and academic qualifications at the Department of Pharmacochemistry (Farmacochemie), Faculty of Chemistry (Scheikunde), Free University (Vrije Universiteit) in Amsterdam. He specialised in Molecular Pharmacology and his main research topics/projects were the characterisation of the pre-synaptic beta-adrenergic receptor in rat vas deferens and the effects of oxidative stress on adrenergic receptors in primary rat hepatocytes.

The department’s philosophy was that binding of drugs to their receptor(s) is determined by the drug’s structure and physico-chemical properties. Structure-activity relationships were used for rational drug design. This theme has been running through Frederik’s career so far (see below).

As a post-doctoral fellow at the Institute of Human Genetics, Faculty of Medicine, Free University in Amsterdam, Frederik studied the effects of oxygen on primary rat hepatocyte cultures. The hypothesis was that the oxygen concentration that are routinely used for tissue culture (i.e. air) is actually supra-physiologic (hyperoxic) and that the resulting oxidative stress induces rapid and irreversible changes in cytochrome P450 levels, oxygen consumption, and mitochondrial metabolism in the freshly isolated hepatocytes.

Frederik then moved to the University of Auckland, New Zealand, the Department of Pharmacology and Clinical Pharmacology at the Medical School, to work on metabolism and enzymology in freshly isolated rat hepatocytes of a novel hypoxia-selective anticancer compound called nitracrine, a nitro-acridine DNA binder.

In 1994 Frederik joined the Section of Oncology, which later merged with the Cancer Research Laboratory, and is now the Experimental Therapeutics Group in the Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, the University of Auckland. One of the main and longstanding areas of research in the Centre is the development of novel anticancer drugs targeting hypoxic (=at low or sub-physiological oxygen concentration) cells in tumours. The rationale behind this is that severe hypoxia is a patho-physiological characteristic of tumours and by designing hypoxia-selective cytotoxins or hypoxia-selective prodrugs one can develop drugs that are tumour-selective. Over the years Frederik has worked on several classes of hypoxia-selective anticancer compounds: nitroaryl quaternary ammonium salts of mechlorethamine (nitrogen mustard), dinitrobenzamide mustards and the dinitrobenzamide aziridine CB-1954, tirapazamine analogues (benzotriazine di-N-oxides), cobalt complexes of nitrogen mustards, AQ4N (Banoxantrone, an aliphatic di-N-oxide prodrug of the topo II inhibitor AQ4), DACA (a mixed topo I/topo II inhibitor), DNA minor groove alkylators of the nitrobenzindoline class (related to CC-1065 and the duocarmycins, natural antibiotics) as well as the nitrogen mustard melphalan and the anti-vascular compound DMXAA (Vadimezan or ASA404).

Frederik has gained extensive experience in many aspects of pharmacology of anticancer compounds, including bioanalysis. In particular, he has developed an algorithm to predict (calculate) the diffusion coefficients (drug transport) in tumour tissue of anticancer compounds based on measured or predicted (calculated) physico-chemical properties: lipophilicity (logP or logD), the number of hydrogen bond donors and acceptors, and molecular weight. This work is based on a three-dimensional tissue culture model (the multicellular layer model) developed in the Centre that mimics the extravascular compartment of tumours and over the years Frederik made a significant contribution to its development. This validated model has been successfully used to predict the activity of hypoxia-selective cytotoxins in human tumour xenograft models.

Recently, Frederik has started to work on 2-nitroimidazole hypoxia markers (e.g. EF5) and his group is now also routinely applying flow cytometry & cell sorting (FACS), immunohisto-chemistry, and laser-scanning confocal microscopy.

Frederik prefers to work in a small dedicated team and enjoys the more personal one-on-one interactions with post-graduate students and research staff. Whenever possible Frederik tries to assist other staff and students in the Centre with advice on statistics, data analysis & graphing, and, occasionally, multi-variate data analysis.

 
 
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