K4DD · Kinetics for Drug Discovery (K4DD)

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.