Residence time of medication on target molecule more important than affinity

The effectiveness of a medication is determined not only by its affinity with the target molecule in the body but also by the time the medication remains bound to the molecule. Leiden researchers have been awarded 15 million euro to head a European consortium to develop innovative medicines based on this new concept.

Better medicines

Professor Ad IJzerman and Dr Laura Heitman of the Medicinal Chemistry group at the Leiden/Amsterdam Centre for Drug Research, together with a European consortium of knowledge institutions and companies, submitted a research proposal in response to a call from the European Union for research to develop innovative medicines based on how long they remain bound to their target. Their proposal was selected from 11 candidates for the Innovative Medicines Initiative.

Lego block

For more than a century pharmacology has applied the rule that a medicine has to fit its target molecule in the body, generally a protein. The idea is that this will guarantee the effectiveness of the medicine. Researchers have been trying for years to find and make molecules that have the required affinity with the target protein, and preferably with not too many other proteins in the body.

One in 15,000

Nonetheless, 90% of the candidate medicines that are carefully selected on the basis of this aim fail in the stage of clinical trials. And only one in 15,000 candidate medicines eventually reach the market. Given that the whole process of drug development takes 15 years, this represents a considerable waste of time and money.

KINOTYPE

Ad IJzerman

A new approach is therefore needed. IJzerman and Heitman will be developing such a novel approach, together with their European KINOTYPE consortium. A crucial new insight is that the time a medicine is bound to a target molecule is more decisive for the effectiveness of the medicine than the affinity between medication and target.

Ideal match

Laura Heitman

The call by the European Union was the ideal match for IJzerman and Heitman. IJzerman: ‘We were absolutely amazed when we read it - this was precisely the theme of the Veni subsidy that Laura received in 2010. We immediately felt as if we were in the driving seat and, with the excellent team that we have put together, we were 'an offer that Brussels couldn't refuse.''

First stage

Together with the pharmaceutical industry in Europe, the consortium is now preparing a definitive proposal to develop over the coming five years methods for determining the so-called 'kinotype' of medicine molecules. This relates to such questions as: how transient is a medicine? How long does it remain bound to the target molecule? The aim of this research is to improve the efficienty of the first phase of medicine research.