Kinetics for Drug Discovery


Start Date
End Date
IMI1 - Call 4
Grant agreement number

IMI Funding
8 286 930
EFPIA in kind
9 831 318
2 868 768
Total Cost20 987 016


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.

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.

Achievements & News

K4DD project results in a PhD thesis
Binding interactions between neuropeptides (the body’s neural signalling molecules), drugs and their target molecules were the focus of the first PhD thesis defence resulting from IMI’s K4DD project. Indira Nederpelt of Leiden University was the author of the thesis which has already resulted in six peer-reviewed publications, with more to come. ###The thesis has helped expand the toolbox of available methods which allow more accessible measurements of how drugs and their target molecules interact in the body. According to Ad IJzerman of Leiden University, K4DD’s managing entity, ‘Indira’s study falls perfectly within K4DD's ambition to transform binding kinetics into traditional, indispensable, drug discovery parameters and thereby improve the success rate of drug discovery in the future.’ The main 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. An important part of the project is its educational programme, which has funded more than 20 post-docs and PhD students in the last five years. The programme has provided fellows with the opportunity to gain a thorough understanding of the connection between drug discovery and drug development by offering them an extensive drug discovery course and several binding-kinetics-oriented symposia. Fellows also got the opportunity to improve their soft skills by taking a scientific writing course, career workshops and a presentation workshop. Several more PhD theses are expected to be successfully defended by the end of this year.
(April 2017)

Save the date: K4DD end meeting in October
In the last five years, IMI’s K4DD project has made a significant contribution to helping scientists understand how drugs bind with their targets in the body. This year the project is coming to a close and will share some of its achievements and lessons learned at a closing conference from 16 to 18 October in Berlin, Germany, ###which will be open to the entire scientific community. The event will feature distinguished speakers from a range of pharmaceutical companies and universities, including Leiden University, the University of Vienna and AstraZeneca. The keynote speech will be delivered by Piet van der Graaf, professor of systems pharmacology at Leiden University and one of the leaders in the field. Registration is now open via the project website.
(March 2017)

New K4DD math formula predicts duration of potential drug effect
When researchers assess potential new drug candidates, it is not only important for them to know whether a particular drug molecule will bind with its biological target in the body, but also with what strength and speed this binding will occur. ###If the binding is weak and short-lived or it takes too long for the molecule to bind with the receptor, the drug won’t be very effective in treating patients. In order to improve the assessment of potential new medicines, K4DD project fellow Wilbert de Witte from the Leiden University has published a new mathematical model which predicts how long a drug effect will last. The model takes into account several important variables such as the concentration of the drug in the body and its rate of binding and unbinding with the biological target, and analyses them in order to predict the duration of the potential drug effect. This mathematical approximation, which was published recently in the journal Trends in Pharmacological Sciences, gives an idea earlier in the drug development process on whether a drug is worth pursuing or not. It has the potential to reduce waste and increase the likelihood of getting better and safer drug candidates for the benefit of patients. ‘Even though only one partner is responsible for this paper, the idea to initiate this particular approach was created during discussions within the consortium,’ said Tale Sliedrecht of Lygature, one of the K4DD project partners. ‘By creating an open, pre-competitive environment, researchers from different areas were able to share their insights and needs. The model we came up with is quite significant: the study has led to a lot of debate within the consortium and was highly appreciated by scientists in K4DD’. The study contributes to the overall goal of the K4DD project which 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. (February 2017)

K4DD study sheds light on drug target for Parkinson’s and cancer
Drugs work by binding with molecules in the body to either block or alter the action of the target molecule. IMI’s K4DD project works to understand this complex and dynamic relationship, and recently the project reported a big step forward ###– a step which could lead to the development of safer and more effective drugs for a broad range of diseases. Two of the K4DD project partners, Leiden University in the Netherlands and a British SME Heptares Therapeutics, worked together to improve the understanding of the so-called adenosine A2A receptor, a therapeutic target for several diseases including Parkinson’s and cancer. Currently many efforts are directed towards discovering new therapeutic molecules which could bind with this receptor, but the desired properties of such molecules are not well understood. By developing a series of molecules, which were similar in structure but had different dynamics of binding with the adenosine A2A receptor, the K4DD partners gained new, significant insights into how this receptor interacts with different molecules. This in turn enabled them to understand factors which cause some potential drug molecules to disconnect from the receptor, knowledge which can probably be applied to similar mechanisms which exist in a broad range of other receptors similar to A2A. This will lead to the development of safer and more effective drugs to target receptors in general. According to the project partners, the collaborative nature of the IMI project was the key to achieving this success. ‘The K4DD project partners have created an open environment in which the sharing of knowledge, results and resources is continuously stimulated’, said Tale Sliedrecht of Lygature, one of the project partners. ‘In this particular study two partners with different specialties combined forces and generated new findings which would not have been possible without the collaboration.’ (November 2016)

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 Show participants on map

EFPIA companies
  • AstraZeneca AB, Södertälje, Sweden
  • Bayer AG, Berlin, Germany
  • F. Hoffmann-La Roche Ltd, Basel, Switzerland
  • Glaxosmithkline Research And Development LTD, Brentford, Middlesex, United Kingdom
  • Janssen Pharmaceutica NV, Beerse, Belgium
  • Merck KGaA, Darmstadt, Germany
  • Sanofi-Aventis Deutschland GMBH, Frankfurt / Main, Germany
Universities, research organisations, public bodies, non-profit groups
  • Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V., München, Germany
  • HITS gGmbH, Heidelberg, Germany
  • Imperial College of Science, Technology and Medicine, London, United Kingdom
  • Ruhr-Universitaet Bochum, Bochum, Germany
  • Stichting VU, Amsterdam, Netherlands
  • Universiteit Leiden, Leiden, Netherlands
  • University of Dundee, Dundee, United Kingdom
  • University of Nottingham, Nottingham, United Kingdom
  • University of Oxford, Oxford, United Kingdom
  • Universität Wien, Vienna, Austria
Small and medium-sized enterprises (SMEs)
  • Heptares Therapeutics Limited, Welwyn Garden City, United Kingdom
  • Sierra Sensors GmbH, Hamburg, Germany
  • Stichting Lygature, Utrecht, Netherlands


Project coordinator
Anke Mueller-Fahrnow
Bayer AG
+49 30 468 17699
Managing entity
Ton Brouwer
Universiteit Leiden
+31 71 5273149