Rasmus Prætorius Clausen

1994: M. Sc. Chemistry - Cell Biology (University of Southern Denmark)
1999: Ph.D. Organic Chemistry (University of Århus)

November 1999- May 2000 Lundbeck A/S
May 2000- Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen

Lundbeck Foundation Fellowship, 2000-2003
Drug Research Academy Fellowship, 2004

Treasurer in European Federation of Medicinal Chemistry (EFMC).

The main object of my research is to develop compounds that affect neurotransmission in the central nervous system in a specific mannner. The aim is to increase the knowledge about neurotransmission in the brain using chemistry focused approaches and eventually could point to new therapeutic strategies. 

Most of the research is currently focused on:

- glutamate receptor ligands 

- GABA uptake inhibitors

Glutamate receptor ligands

Design and synthesis of small molecule glutamate receptor ligands is a key area. New ligands that affect the glutamatergic system in a selective manner are designed and synthesised. Molecular modelling is applied in the design of compound series and in the interpretation of the pharmacological behaviour of new ligands.  The research is also moving towards making larger ligands, in example dimers of classical ligands. This can give molecules which behave differently than the smaller monomeric parts, and lead to novel pharmacological tools and therapeutic candidates. Thus, we are currently developing building blocks that can be employed in these strategies. 

GABA uptake inhibitors
Four different subtypes (GAT1-4) of GABA transporters are responsible for transport of the inhibitory neurotransmitter GABA. Despite intense efforts, only one of these transporters (GAT1) can be targeted selectively by previous inhibitors of GABA uptake. The recent development of a compound (EF1502) with preference for both GAT1 and GAT2 has indicated the importance of the transporter subtype GAT2 and the development of new selective GABA uptake inhibitors therefore have an unexploited potential.

Other current research areas are epigenetic modulators, GHB analogues, enzymatic modification of proteins, synthetic methods for amino acids. 

The most recent publications:

(all publications click here)

S. D. Nielsen, M. Fulco, M. Serpi, B. Nielsen, M. B. Hansen, K. L. Hansen, C. Thomsen, R. Brodbeck, H. Bräuner-Osborne, R. Pellicciari, P.-O. Norrby, J. R. Greenwood, and R. P. Clausen. A highly selective agonist for the metabotropic glutamate receptor mGluR2. MedChemComm, 2011, in press.

B. Lohse, A. L. Nielsen, J. B. Kristensen, C. Helgstrand, P. A. C. Cloos, L. Olsen, M. Gajhede, R. P. Clausen, and J. L. Kristensen. Targeting Histone Lysine Demethylases by Truncating the Histone 3 Tail to Obtain Selective Substrate-Based Inhibitors. Ang. Chem. Int. Ed., 2011, 50, 9100-9003.

J. B. L. Kristensen, A. L. Nielsen, L. Jørgensen, L. H. Kristensen, C. Helgstrand, L. Juknaite, J. S. Kastrup, J.L. Kristensen, R. P. Clausen, L. Olsen and M. Gajhede. Selectivity of ligands targeting oncogenic histone demethylases towards tumor repressor UTX. FEBS Lett., 2011, 585, 1951-1956.

P. D. Skottrup, P. Leonar, J. Z. Kaczmarek, F. Veillard, J. Enghild, R. O’Kennedy, A. Sroka, R. P. Clausen, J. Potempa, E. Riise. Diagnostic evaluation of a nanobody with picomolar affinity towards the protease RgpB from Porphyromonas gingivalis. Anal. Biochem., 2011, 415, 158-167.

B. Lohse, J. L. Kristensen, L. H. Kristensen, K. Agger, K. Helin, M. Gajhede, R. P. Clausen. Inhibitors of histone demethylases. Bioorg. Med. Chem., 2011, 19, 3625-3636.

S.B. Vogensen, J.R. Greenwood, L. Bunch and R. P. Clausen. Glutamate Receptor Agonists: Stereochemical Aspects. Curr. Top. Med. Chem. 2011, 11, 887-906.

K. K. Madsen, B. Ebert, R. P. Clausen, P. Krogsgaard-Larsen, A. Schousboe and H. S. White. The selective GAT inhibitors tiagabine and N-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-hydroxy-4-(methylamino)-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol (EF1502) exhibit mechanistic differences in their ability to modulate the ataxia and anticonvulsant action of the extrasynaptic GABA_A receptor agonist gaboxadol. J. Pharmacol. Exp. Ther., 2011, 338, 214-219.

A.C. Lehre, N.M. Rowley, Y. Zhou, S. Holmseth, C. Guo, T. Holen, R. Hua, P. Laake, A.M. Olofsson, I. Poblete-Naredo, D.A. Rusakov, K.K. Madsen, R.P. Clausen, A. Schousboe, H.S. White, N.C. Danbolt. Deletion of the betaine-GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult mice. Epilepsy Res., 2011, 95, 70-81.

R. Risgaard, K.B. Hansen and R. P. Clausen. Partial agonists and subunit-selectivity at NMDA receptors. Chemistry – A European Journal 2010, 16, 13910-13918.

K. Frydenvang, D.S. Pickering, J.R. Greenwood, N. Krogsgaard-Larsen, L. Brehm, B. Nielsen, S.B. Vogensen, H. Hald, J.S. Kastrup, P. Krogsgaard-Larsen and R. P. Clausen. Biostructural and pharmacological studies of bicyclic analogues of the 3-isoxazolol glutamate receptor agonist, ibotenic acid. J. Med. Chem., 2010, 53, 8354–8361.

J. J. Bornholdt, J. Felding, R. P. Clausen, and J. L. Kristensen. Ring opening of pymisyl protected aziridines with organocuprates. Chemistry – A European Journal 2010, 16, 12474–12480.

P. Wellendorph, S. Høg, P. Sabbatini, S., M. H. F. Pedersen, L. Martiny, G. M. Knudsen, B. Frølund, R. P. Clausen, and H. Bräuner-Osborne. Novel radioiodinated GHB analogues for radiolabeling and photolinking of high-affinity GHB binding sites. J. Pharmacol. Exp. Ther., 2010, 335, 458-464.

P. Sabbatini, P. Wellendorph, S. Høg, S., M. H. F. Pedersen, H. Bräuner-Osborne, L. Martiny, B. Frølund, and R. P. Clausen. Design, Synthesis, and in Vitro Pharmacology of New Radiolabeled γ-Hydroxybutyric Acid Analogues Including Photolabile Analogues with Irreversible Binding to the High-Affinity γ-Hydroxybutyric Acid Binding Sites. J. Med. Chem., 2010, 53, 6506–6510.

R. P. Clausen, P. Naur, A. S. Kristensen, J. R. Greenwood, M. Strange, H. Bräuner-Osborne, A. A. Jensen, A. S. T. Nielsen, U. Geneser, L. M. Ringgaard, B. Nielsen, D. S. Pickering, L. Brehm, M. Gajhede, P. Krogsgaard-Larsen, J. S. Kastrup. The glutamate receptor GluR5 agonist (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid and the 8-methyl analogue: Synthesis, molecular pharmacology and biostructural characterization. J. Med. Chem., 2009, 52, 4911-4922.

K. K. Madsen, R. P. Clausen, O. M. Larsson, P. Krogsgaard-Larsen, A. Schousboe and H. S. White. Synaptic and extrasynaptic GABA transporters as targets for anti-epileptic drugs. J. Neurochem., 2009, 109, 139-144.

P. Sivaprakasam, O. David, K.B. Hansen, B. Nielsen, S.F. Traynelis  R.P. Clausen, F. Couty and L. Bunch. Stereocontrolled Synthesis and Pharmacological Evaluation of Azetidine 2,3-Dicarboxylic Acids at NMDA Receptors. ChemMedChem, 2009, 4, 110-117.

Other publications

R.P. Clausen, M.T. Pedersen, K. Helin. Histone demethylases. In Methods and Principles in Medicinal Chemistry: Epigenetic Targets in Drug Discovery, 2009, 42, 269-290. (book chapter)

K. Madsen, H.S. White, R.P. Clausen, B. Frølund, O.M. Larsson, P. Krogsgaard-Larsen, A. Schousboe. Functional and Pharmacological Aspects of GABA Transporters. Handbook Of Neurochemistry And Molecular Neurobiology: Neural Membranes and Transport, 2007 (book chapter)

in Danish:

J. Kristensen, B. Lohse og R. P. Clausen. Histonehaler – et nyt mål indenfor kræftbehandling. Lægemiddelforskning, 2010, in press

R. P. Clausen, R. Risgård, S. D. Nielsen, J. Kristensen og K. B. Hansen. Nye NMDA-receptor-ligander til udforskning af hjernen. Dansk Kemi, 2010, 91, 21-23.

R. P. Clausen, S. D. Nielsen, J. Kristensen og K. B. Hansen. Ind i hjernen med nye stoffer. Lægemiddelforskning, 2009.

K. K. Madsen, R. P. Clausen, O. M. Larsson og A. Schousboe. GABA-transportører – håb om bedre epilepsibehandling. Lægemiddelforskning, 2008.

S. Høg, P. Wellendorph, J. R. Greenwood og R. P. Clausen. Hvordan virker Fantasy i hjernen? Lægemiddelforskning, 2005.