13th EFMC Short Course on Medicinal Chemistry

Helena Danielson is Professor of Biochemistry at Uppsala University in Sweden since 2002 and a specialist in enzymology and biosensor-based drug discovery. Training and career: Helena Danielson received a Master of Science in Chemical Engineering at Lund University in 1982 and, as a Fulbright scholar, she received a Master of Science in Biochemistry, University of Rochester, Rochester, NY, USA in 1984, and thereafter a Ph. D. in Biochemistry at Stockholm University in 1987. As a postdoc at Karolinska Institutet in Stockholm Helena Danielson started a research project on HIV protease as a drug target for AIDS, and has since expanded her research to other enzymes and diseases, more recently also with an interest in membrane receptors and neurological drug targets. She has been at Uppsala University since 1988. Scientific profile: Helena Danielson has focused on developing enzymology for drug discovery, and in particular biomolecular interaction analysis for detailed studies of enzyme-inhibitor interactions and other important recognition processes in the life science area. Her work has involved studies of a variety of enzymes, primarily proteases and polymerases from viruses and other infectious organisms, and other proteins involved in important disease processes. She has extensive experience of the commercial drug discovery process through >25 years of collaborative research with partners in pharmaceutical and biotechnological industry. An important collaboration with Biacore AB was initiated in 1997 and has resulted in adapting biosensor technology for drug discovery and the development of new biosensor products for the drug discovery industry. Entrepreneurial achievements: Helena Danielson co-founded Beactica AB in 2006 and was Chief Scientific Officer until 2014. The company is a specialist drug discovery company that generates novel drug leads from low molecular weight fragments by integrating biomolecular interaction analysis with in silico molecular docking techniques.

Dr. Elizabeth de Lange obtained her PhD from Leiden University in 1993, and was tenured in 2004. She is the Head of Translational Pharmacology at Leiden Academic Center for Drug Research (LACDR). Her ultimate aim is to aid in the prediction of the dose-response relationship of CNS drugs in the clinical setting, on the basis of preclinical data (translational research). Her research involves the identification and characterization of the rate and extent of key factors in the dose-response relationship of mainly CNS drugs in health and CNS disorders. It involves the use of advanced preclinical research (e.g. including microdialysis, EEG monitoring, PET scanning) and advanced mathematical modelling and simulations (Systems Pharmacology approach). She has published more than 100 papers and book chapters and She is a frequently invited lecturer. Furthermore, Dr de Lange is a member of the Editorial Board of FBCNS, co-founded and (co-) chaired several of the International Symposia on Microdialysis in Drug R&D. She has been the Chair of the Organizing Committee of the 9th International Cerebrovascular Biology (CVB), Conference. Furthermore, she was the 2014 Chair of the Annual Meeting Programming Committee of the American Association of Pharmaceutical Scientists (AAPS), after many other functions within this professional organization with ~10.000 members. She is honoured as AAPS Fellow since 2013. Her company In Focus provides courses, training and advice on microdialysis, pharmacokinetics, blood-brain barrier transport, and CNS target site distribution and effects, and systems pharmacology (info@infocus-ecmdelange.nl)

Wilbert de Witte is doing his PhD research in the Pharmacology division of the Leiden Academic Centre for Drug Research since 2013. His research aims to identify the influence of drug-target binding kinetics on in vivo drug effect by using modelling and simulation techniques. To identify this influence, drug-target binding kinetics are integrated with the other drivers of in vivo effects including pharmacokinetics, rebinding and target turnover. As this research is part of the IMI Kinetics for Drug Discovery (K4DD) consortium, the obtained modelling and simulation results are generalized to result in useful insights that can be applied in drug discovery. Wilbert obtained both his bachelor’s and master’s degree in Bio-Pharmaceutical Sciences at Leiden University.

Director of the department for Molecular Interaction and Biophysics (MIB) at Merck.
The current research includes Fragment based lead discovery approaches, thermodynamic signatures, interaction kinetics, protein dynamics and structures to support medicinal chemistry. Former scientific work was done on protein kinases at the Friedrich Miescher Institute /Novartis in Basel on protein kinases. Postdoctoral research as EMBO fellow at the CNRS Institute IPMC in Sophia Antipolis / France working on nucleotide exchange factors and adaptor proteins in p21ras signalling.
Biophysical and biochemical education in the department of Biophysics at the Max Planck Institute in Heidelberg focusing on p21ras and p21ras like proteins

Laura H. Heitman, PhD. is a tenured associate professor of Molecular Pharmacology at the Division of Medicinal Chemistry at the Leiden Academic Centre for Drug Research (LACDR, Leiden University), after being appointed as ‘tenure track’ assistant professor in January 2009. She obtained her PhD degree in April 2009 for her thesis on “Allosteric modulation of ‘reproductive’ GPCRs” in collaboration with Organon/MSD (Oss, The Netherlands). Her research interests are mainly focused on understanding and improving drug-receptor interactions, and more specifically, target binding kinetics and allosteric modulation of GPCRs. In the last couple of years, she has obtained several competitive research grants (e.g. IMI-Kinetics for Drug Discovery/K4DD), all allowing her to study these novel, clinically relevant and highly translational concepts for drug action. Her research activities have currently led to an authorship on over 50 papers in this field.

Ad IJzerman holds the position of full professor of medicinal chemistry at the Leiden Academic Centre for Drug Research (Leiden University). He obtained his PhD degree on the medicinal chemistry of the beta-adrenergic receptor. Ever since, he has had a strong interest in novel concepts for ligand intervention of G protein-coupled receptor activity, such as allosteric modulation, receptor constitutive activity and, more recently, drug-target binding kinetics, including residence time. Ad was a co-author on the seminal 2008 Science paper elucidating the structure of the adenosine A2A receptor, with a follow-up in a 2012 Science report. He was awarded on quite a number of occasions, both for his research and his teaching. He is the author of over 300 papers, inventor on a dozen patents, and has been or is a member of the editorial boards of the main medicinal chemistry journals, including the Journal of Medicinal Chemistry.

Dr. Vauquelins’ initial research interest dealt with the purification of beta-adrenergic receptors, then with the discrimination between agonist- and antagonist- receptor interactions and then with their regulation by physiologic and patho-physiologic conditions. Among others, this work shed light on the benefits of intact cell system and on the important role continuing target occupancy (residence time) for optimal drug therapy. Presently, simulations are performed to scrutinize the contribution of bivalency (and multi-step binding in general) and the participation of the cell membrane and drug rebinding phenomena to this end.