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K4DD

Kinetics for Drug Discovery

Summary

Drugs work by binding with molecules in the body and to either block or alter the action of the target molecule. The goal of the K4DD project is to improve our understanding of how potential drugs bind with their target, and develop methods and tools to allow researchers to study drug-target interactions with greater ease. These tools would help researchers to determine whether a drug candidate is likely to be safe and effective much earlier in the drug development process.

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The difficulties of drug development

A major difficulty for those attempting to develop new medicines is predicting whether or not a potential drug will be effective in humans. The laboratory tests used to evaluate this today are simply not accurate enough.

Currently, researchers spend a lot of time studying how strongly a potential drug binds with its target. However, less attention is given to the question of how long the drug remains bound to the target.

Nevertheless, there is mounting evidence to suggest that the kinetics of the interaction between a drug and its target have a strong influence on the clinical success of a drug. For example, studies have shown that many recently-marketed drugs have improved kinetic profiles. This is logical; as drugs only work when they are bound to the target, the lifetime of the drug-target complex is key to the success of a drug.

Towards a better understanding of binding kinetics

Today, a lot of the expertise and data on binding kinetics is scattered across numerous smaller projects, institutions and organisations. By bringing together these diverse groups, K4DD is set to give a major boost to this important area of drug development.

The first goal of the K4DD team is to enhance our understanding of binding kinetics; exactly how do small molecules interact with their targets?

Ultimately, the project aims to develop a range of robust techniques, methods and models that could be easily incorporated into the drug development pathway and enable scientists and drug designers worldwide to reliably predict a molecule’s kinetic properties (its ‘kinotype’). This information will allow drug developers to more easily determine the safety and efficacy of a molecule. In the long run, this will weed out ineffective or unsafe molecules earlier in the drug development process.

Finally, the project also hopes to raise awareness of the importance of considering the kinetic aspects of drug-target interactions throughout drug development.

For patients, the benefits of K4DD lie in its efforts to speed up and improve the drug development process.

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Achievements & News

K4DD professor knighted
Meindert Danhof, Professor of Pharmacology at the University of Leiden and a partner in IMI’s K4DD project has been appointed as Knight in the Order of the Netherlands Lion. Professor Danhof received the royal decoration for ###his research and development of models that have made an important contribution to better predicting the efficacy of medicinal products.
Within the K4DD project framework, Professor Danhof's group, together with other academic and pharmaceutical industry research groups, focuses on better understanding the kinetics of the interaction between a drug molecule and its disease target within the human body. There is growing evidence that this kinetic information is important to predict how fast a drug effect will appear in a patient, and how long it will last.
Translating research findings from the ‘test tube’ stage to the clinical stage requires comprehensive pharmacological models. These models not only need to take into account the interaction of a drug with its disease target at a cellular level, but also to account for the human body’s reaction to the drug. Ultimately, the aim of pharmacological models developed within K4DD is to further optimise the prediction of the efficacy of medicinal products early on in the drug discovery process.
(June 2014)

Participants

EFPIA

  • Bayer Pharma AG, Berlin, Germany
  • AstraZeneca AB, Sodertalje, Sweden
  • F. Hoffmann-La Roche AG, Basel, Switzerland
  • GlaxoSmithKline Research and Development Ltd, Brentford, UK
  • Janssen Pharmaceutica NV, Beerse, Belgium
  • Merck KGaA, Darmstadt, Germany
  • Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany

Universities, research organisations, public bodies, non-profit groups

  • Universiteit Leiden, Leiden, Netherlands
  • Foundation Top Institute Pharma (Stichting Top Instituut Pharma), Leiden, Netherlands
  • Imperial College Of Science, Technology & Medicine, London, UK
  • Ruhr-Universität Bochum, Bochum, Germany
  • Stichting VU-VUMC , Amsterdam, Netherlands
  • Universität Wien, Vienna, Austria
  • University of Dundee, Dundee, UK
  • University of Nottingham, Nottingham, UK
  • University of Oxford, Oxford, UK

SMEs

  • European Screening Port GmbH, Hamburg, Germany
  • Heptares Therapeutics Limited, Welwyn Garden City, UK
  • HITS gGmbH, Heidelberg, Germany
  • Sierra Sensors GmbH, Hamburg, Germany

Facts & Figures

Start date 01/11/2012
Duration 60 months
   
Contributions   €
IMI funding   8 300 000
EFPIA in kind   9 800 000
Other   2 800 000
Total cost 20 900 000

Links and Documents

IMI Funding per participant

Contact

Project Coordinator
Anke Müller-Fahrnow

Bayer Pharma AG
Tel: +49 30 4681 7699
E-mail: anke.mueller-fahrnow[AT]bayer.com

Managing Entity
Ad Ijzerman

Universiteit Leiden
Tel: +31 71 5274651
E-mail: ijzerman[AT]lacdr.leidenuniv.nl