Ad IJzerman | Medicinal Chemistry

Universiteit Leiden

Ad IJzerman, Prof.

Position:

Professor of Medicinal Chemistry and Head of division

Telephone number: +31 (0)71 527 4651
E-mail address: ijzerman@lacdr.leidenuniv.nl
Faculty/Unit: Faculty of Science, Leiden/Amsterdam Center for Drug Research, Medicinal Chemistry
Office address: Gorlaeus Laboratories
Einsteinweg 55
2333 CC Leiden

Biography: I studied pharmacy at Utrecht University. In 1979 I graduated with a specialisation in pharmaceutical chemistry and one year later I qualified as a pharmacist. Rather than opening a drug store I continued my research education, leading to the defense of my PhD thesis from the Vrije Universiteit in Amsterdam in 1985, on a subject in the area of receptor research. I was appointed assistant, associate and full professor of medicinal chemistry in Leiden in 1985, 1992 and 2000, respectively.

My research interests have always been linked to G protein-coupled receptors (GPCRs). In particular the molecular mechanisms of drug action are at the core of my research 'business'. One cannot study all (800?) GPCRs at the time, so my main attention is focussed on adenosine receptors. Every now and then I allow myself to diverge a little bit, lately to study nicotinic acid receptors. All this has led to a scientific 'output' of over 220 articles, quite a few reviews and book chapters, and some 20 accepted PhD theses. You will find references to recent work at this website.

Duties as a professor include teaching, which I like very much. My hope and dream is that once I will be able to show my students the wonder world of drug - receptor interactions through some sort of 'molecular microscope'. Next to these teaching efforts other 'obligations' are the membership of the editorial boards of the Journal of Medicinal Chemistry, ChemMedChem, Purinergic Signalling, Chemistry & Biodiversity, Drug Development Research, Molecular Informatics, and Molecules. I happily contribute to the IUPHAR adenosine receptor, GnRH, and nicotinic acid receptor nomenclature committees, and manage(d) quite a number of receptor-related research programs funded by Dutch scientific bodies such as the Top Institute Pharma, and by the European Commission. I also served as chairman to FIGON, the Dutch federation for innovative drug research (www.figon.nl).

In Press

Lane, R., Klein Herenbrink, C., Van Westen, G.J.P., Spoorendonk, J.A., Hoffmann, C., IJzerman, A.P. , A Novel Non-ribose Agonist, LUF5834, Engages Distinct Residues from that of Adenosine-like Ligands to Activate the Adenosine A2A Receptor, Molecular Pharmacology.

Du, L., Gao, Z-G., Nithipatikom, K., IJzerman, A.P., van Veldhoven, J.P., Jacobson, K.A., Gross, G.J., Auchampach, J.A. , Protection from myocardial ishchemia/reperfusion injury by a positive allosteric modulator of the A3 adenosine receptor, Journal of Pharmacology and Experimental Therapeutics, vol. 340.

Peeters, M.C., Li, Q., van Westen, G.J.P., IJzerman, A.P. , Three “hotspots” important for adenosine A2B receptor activation: a mutational analysis of transmembrane domains 4 and 5 and the second extracellular loop , Purinergic Signalling.

2012

Vilums, M., Overman, J., E., K., Scheel, O., Brussee, J., IJzerman, A.P. , Understanding of molecular substructures that contribute to hERG K+ channel blockade: synthesis and biological evaluation of E-4031 analogues, ChemMedChem, vol. 7, pp. 107-113.

2011

Göblyös, A., IJzerman, A.P. , Allosteric modulation of adenosine receptors, Biochimica et Biophysica Acta (BBA) - Biomembranes, vol. 2011, pp. 1309-1318.

Jacobson, K.A., Gao, Z-G., Göblyös, A., IJzerman, A.P. , Allosteric modulation of purine and pyrimidine receptors, Advances In Pharmacology, vol. 61, pp. 187-220.

Bajramovic, J.J., van der Putten, C., Zuiderwijk-Sick, E.A., van Straalen, L., de Geus, E.D., Boven, L.A., Kondova, I, IJzerman, A.P. , A new role for adenosine A3 receptors in chronic neuroinflammation, Glia, vol. 59, issue 1, pp. 151-152.

van der Horst, E., Peironcely, J.E., van Westen, G.J.P., van den Hoven, O.O., Galloway, W.R.J.D., Spring, D.R., Wegner, J.K., van Vlijmen, H.W.T., IJzerman, A.P., Overington, J.P., Bender, A. , Chemogenomics Approaches for Receptor Deorphanization and Extensions of the Chemogenomics Concept to Phenotypic Space , Curr. Top. Med. Chem, vol. 11, issue 15, pp. 1964-1977.

Verzijl, D., IJzerman, A.P. , Functional selectivity of adenosine receptor ligands, Purinergic Signalling, vol. 7, pp. 171-192.

Gao, Z.G., Verzijl, D., Zweemer, A., Ye, K., A., G., A.P., I., Jacobson, K.A. , Functionally biased modulation of A(3) adenosine receptor agonist efficacy and potency by imidazoquinolinamine allosteric enhancers, Biochemical Pharmacology, vol. 82.

Peeters, M.C., van Westen, G.J.P., Guo, D., Wisse, L.E., Müller, C.E., Beukers, M.W., IJzerman, A.P. , GPCR structure and activation: an essential role for the first extracellular loop in activating the adenosine A2B receptor, FASEB J, vol. 25, issue 2, pp. 632-643.

Gomes, I, A.P., I., K., Y., E.L., M., L.A., D. , G protein-coupled receptor heteromerization: a role in allosteric modulation of ligand binding, Molecular Pharmacology, vol. 79, issue 6, pp. 1044-1052.

Fruh, V., IJzerman, A.P., Siegal, G. , How to catch a membrane protein in action: a review of functional membrane protein immobilization strategies and their applications, Chemical Reviews, vol. 111, issue 2, pp. 640-656.

Heitman, L.H., Kleinau, G., Krause, G., Brussee, J., IJzerman, A.P. , Identification of a second allosteric site at the luteinizing hormone receptor that recognizes both allosteric enhancers and inhibitors, British Journal of Pharmacology.

Fredholm, B.B., IJzerman, A.P., Jacobson, K.A., Linden, J., Müller, C.E. , International union of basic and clinical pharmacology. LXXXI. Nomenclature and classification of adenosine receptors. An update, Pharmacological Reviews, vol. 63, issue 1, pp. 1-34.

Offermanns, S., Colletti, S.L., Lovenberg, T.W., Semple, G., Wise, A., IJzerman, A.P. , International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B), Pharmacological Reviews, vol. 63, issue 2, pp. 269-290.

van Westen, G.J.P., Wegner, J.K., IJzerman, A.P., van Vlijmen, H.W.T., Bender, A. , Proteochemometric Modeling as a Tool to Design Selective Compounds and for Extrapolating to Novel Targets, Med. Chem. Commun., vol. 2, pp. 16-30.

Blad, C.C., von Frijtag Drabbe Künzel, J.K., de Vries, H., Mulder-Krieger, T., Bar-Yehuda, S., Fishman, P., IJzerman, A.P. , Putative role of the adenosine A(3) receptor in the antiproliferative action of N (6)-(2-isopentenyl)adenosine, Purinergic Signalling, vol. 7, pp. 453-462.

van Veldhoven, J.P.D., Blad, C.C., Artsen, C.M., Klopman, C., Wolfram, D.R., Abdelkadir, M.J., Lane, J.R., Brussee, J., IJzerman, A.P. , Structure-Activity Relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A), Bioorg.Med.Chem.Lett, vol. 21, issue 9, pp. 2736-2739.

Peeters, M.C., van Westen, G.J.P., Li, Q., IJzerman, A.P. , The importance of the extracellular loops in G protein-coupled receptors for ligand recognition and receptor activation, TiPS, vol. 32, issue 1, pp. 35-42.

Lane, J.R., Jaakola, V.P., IJzerman, A.P. , The structure of the adenosine receptors implications for drug discovery, Advances in Pharmacology, vol. 61, pp. 1-40.

Van Westen, G.J.P., Wegner, J.K., Geluykens, P., Kwanten, L., Vereycken, I, Peeters, A., IJzerman, A.P., Van Vlijmen, H.W.T., Bender, A. , Which Compound to Select in Lead Optimization? Prospectively Validated Proteochemometric Models Guide Preclinical Development, PLoS ONE, vol. 6, issue 11, pp. e27518.

2010

Doddareddy, M.R., Klaasse, E.C., Shagufta, ., IJzerman, A.P., Bender, A. , Prospective Validation of a Comprehensive In silico hERG Model and its Applications to Commercial Compound and Drug Databases, ChemMedChem, vol. 5, no. 5, pp. 716-729.

van der Horst, E., Peironcely, J., IJzerman, A., Beukers, M., Lane, J., van Vlijmen, H., Emmerich, M., Okuno, Y., Bender, A. , A novel chemogenomics analysis of G protein-coupled receptors (GPCRs) and their ligands: a potential strategy for receptor de-orphanization, BMC Bioinformatics, vol. 11, no. 1, pp. 316.

Lane, J.R., Klaasse, E., van Bruchem, J., Beukers, M.W., IJzerman, A.P. , Characterization of [(3)H]LUF5834: A novel non-ribose high-affinity agonist radioligand for the adenosine A(1) receptor, Biochem Pharmacol , vol. 80, issue 8, pp. 1180-1189.

Ad currently supervises the following students:

15/08/2009

Medicinal Chemistry