Monday 19 July 2010

Two Expert Opinion authors are awarded young researchers' prizes by EFMC

The European Federation for Medicinal Chemistry has awarded prizes to two Expert Opinion authors.
Dr Andreas Bender received the EFMC prize for young researchers in academia. Dr Bender published recently a review in Expert Opinion on Drug Discovery on "Computational methods to support high-content screening: from compound selection and data analysis to postulating target hypotheses" and is presently preparing a perspective article entitled "How similar are those molecules after all? Use two descriptors and you will have three different answers."
Dr Antonio Nardi is the winner of the prize for young researchers in industry. Dr Nardi contributed a couple of review articles on potassium channel openers to Expert Opinion on Therapeutic Patents in 2007 and 2008.
Details of the announcement and a lab presentation by the authors is available on the EFMC's website at http://www.efmc.info/medchemwatch-2010-2/lab.php.

Friday 9 July 2010

Author interview on ‘Taking advantage of tumor cell adaptations to hypoxia for developing new tumour markers and treatment strategies

Peter Ebbesen, Erik O. Pettersen, Thomas A. Gorr, Gerhard Jobst, Kaye Williams, Jochen Kieninger, Roland H. Wenger, Silvia Pastorekova, Ludwig Dubois, Philippe Lambin, Brad G. Wouters, Twan Van Den Beucken, Claudiu T. Supuran, Lorenz Poellinger, Peter Ratcliffe, Arvydas Kanopka, Agnes Görlach, Max Gasmann, Adrian L. Harris, Patrick Maxwell, and Andrea Scozzafava

Dr Claudiu Supuran works at the University of Florence in the department of bioorganic chemistry, and is also an Associate Editor for the Journal of Enzyme Inhibition and Medicinal Chemistry. His research focuses on medicinal chemistry, design of enzyme inhibitors and activators, heterocyclic chemistry, chemistry of sulfonamides, sulfamates and sulfamides, biologically active organo-element derivatives, QSAR studies, X-ray crystallography of metallo-enzymes, metal complexes with biologically active ligands (metal-based drugs), carbonic anhydrases, cyclooxygenases, serine proteases, matrix metalloproteinases, bacterial proteases, and amino acid derivatives among others. He has published more than 600 original research papers in these fields, several patents and two books. Dr Supuran was a co-author of the above paper, and provides an overview of the research and article below.

What was the EUROXY programme and what were the aims of the research?
An integrated EU 6th Framework project which started in 2004 and ended in 2009, termed EUROXY, demonstrated that several biochemical pathways are involved in the transcriptional and translational control of the hypoxic cell phenotype, and evidenced the crosstalk between the many proteins involved in it with responses to pH and redox changes. All these issues are highly significant for the management (treatment and imaging) of hypoxic tumors, and the main scope of this project was just to find such pathways, which are the important enzymes/transcription factors involved in it, and how can they be targeted for eventually finding new drug targets (it would be too ambitious to think we can find a new drug in such a short period of time). The project involved many partners, including Aalborg University, Oslo University, University of Zurich, University of Manchester, University of Florence, University of Oxford, University of Freiburg, Slovak Academy of Sciences – Institute of Virology, Karolinska Institute, University of Maastricht, Lithuanian Institute of Biotechnology, Technical University München, Imperial College, London, as well as several small companies such as, among others, Jobst Technologies.

Could you briefly summarise the key findings of the EUROXY research and their significance?
EUROXY was a highly scientifically successful project. Several hundred original papers were published in the 5 years of the project by the members of this consortium, which led to a much deeper understanding of hypoxia and more precisely to its relevance in cancer. One of the most important finding was that carbonic anhydrase IX (CA IX), one of the enzymes/proteins involved in pH regulation, cell-to-cell contact and other processes that are dysregulated in hypoxic tumors, is a drug target which is useful both for the treatment (as its inhibition leads to a normalization of the tumor pH) and imaging of hypoxic tumors (as, for example, fluorescent CA IX inhibitors bind to the enzyme specifically only in the hypoxic cells over expressing this enzyme, otherwise found in small amounts in normal tissues).

Are there any planned follow up studies or future developments into therapeutic applications of the research findings? Fortunately this project is continuing, under the name of METOXIA, in FP7, being financed by EU for a further 5 years. METOXIA uses many of the great results we obtained in EUROXY, first of all for understanding metastasis of primary hypoxic tumors. The CA IX inhibitors which were initially investigated in EUROXY are now evaluated in animal models with the real hope this time to develop new treatment strategies or imaging of hypoxic tumors.

Why do you think the EUROXY research has been highly cited?
Cancer cells in hypoxic areas of solid tumors are to a large extent protected against the action of radiation as well as many chemotherapeutic drugs, and thus do not respond well to radio- or chemotherapy. Furthermore, many of the basic aspects (biochemistry, molecular biology, physiology) of these cells are poorly understood. EUROXY shed some light on many of these issues, and came up with an alternative to classical chemotherapy: development of CA IX selective inhibitors to be used (in combination therapy) with other agents for the management of these tumors. In addition, pharmacological agents of the same class might be used also for the imaging of such tumors. Thus, we brought new understanding of basic scientific issues together with possible solutions for the management (treatment and imaging) of a type of tumors with poor prognosis.