Objective
There is mounting evidence that the often ignored kinetic aspects of the interaction between a drug and its target are highly relevant for clinical success. This ignorance may be one of the reasons for the high attrition rates in drug discovery, as it has been analyzed that many recently marketed drugs had indeed improved kinetic profiles.
This hindsight knowledge needs to be converted into data-driven guidelines and easily accessible high-throughput assays for future drug discovery and fuels the K4DD consortium of over 20 partners, EFPIA members, universities, research institutes and SMEs. Our integrated approach will lead to the definition of any compound in terms of its target ‘kinotype’, next to affinity and selectivity. For us, integration means analyzing the kinetic behavior of different targets (GPCRs, kinases, proteases) across the three work packages. The partners in the consortium are European key players: they elucidate(d) structures of GPCRs and kinases, are at the forefront of bioanalytical techniques, e.g. surface plasmon resonance, are world-leaders in PKPD modeling, and bring the best of computational resources for e.g. molecular dynamics calculations. Thus, we study the drug-target interaction from picoseconds to >hours, for both soluble and membrane-bound proteins.
At the end of the consortium’s lifetime we anticipate that kinetic aspects of the drug-target interaction can routinely be studied in robust and accessible assays within and outside the consortium, that editors and reviewers routinely ask for a compound’s kinetic data next to its affinity and selectivity, that ‘kinotypic’ knowledge helps define the target product profile and guide the subsequent lead finding and optimization process, and that kinetic guidelines for predictive PKPD modeling approaches are the logical consequence of our efforts.
Thus, the overall ambition of the consortium is to instill lasting kinetic awareness into the pharma community.
Fields of science
Call for proposal
IMI-JU-04-2011
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Coordinator
51373 Leverkusen
Germany
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Participants (20)
2311 EZ Leiden
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1081 HV Amsterdam
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DD1 4HN Dundee
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69118 Heidelberg
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OX1 2JD Oxford
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SW7 2AZ LONDON
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CB21 6DG Cambridge
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NG7 2RD Nottingham
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44801 Bochum
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Participation ended
22525 Hamburg
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20251 Hamburg
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151 85 Sodertaelje
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WC1A 1DG LONDON
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2340 Beerse
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64293 Darmstadt
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4070 Basel
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65929 Frankfurt Am Main
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3521 AL Utrecht
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1010 Wien
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80686 Munchen
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