Rethinking drug discovery
Laura Heitman has been awarded a VIDI grant for her innovative drug research. Heitman strives to optimize a drug’s binding kinetics at its target in order to ultimately fight diseases effectively. She even pleads for a paradigm shift in drug discovery.
Heitman tells the discovery of new medicines is a tedious and lengthy process. Over 10,000 molecules on average need to be studied for one to become a drug and reach the market and ultimately, the patient. The molecules are tested for certain properties, in order to predict whether they are a good medicine. Next, drugs are tested in very costly clinical trials with human volunteers and patients. Still, candidate drugs often fail due to side effects or lack of efficacy. ‘Apparently’, Heitman explains, ‘traditional pharmacological parameters on which we are testing are insufficient to predict a drug’s performance in humans.’ She therefore now wants to explore new parameters.
Binding makes it work
With recent studies, researchers investigated a large number of drugs that are already on the market. The studies suggest that the beneficial effects of these drugs may result from optimal target binding kinetics. Binding kinetics say something about the binding between drugs and the active site in the body. Usually, this is a protein on or in a cell. With bad binding kinetics, drugs quickly lose their binding to the active side in the body, and thus have little time to be effective.
A new paradigm
Heitman wants to investigate how she can optimize the target binding kinetics of drugs. She believes that binding kinetics can become a new measure to predict whether a drug will work or not. And, that this novel parameter constitutes an urgently needed paradigm shift in drug discovery. ‘With the Vidi grant, I intend to study target binding kinetics in a physiologically and pharmacologically relevant setting’, she says. The research focuses on selected G protein-coupled receptors (GPCRs) in the body. This protein family is currently the most exploited and successful class of drug targets.
Heitman hopes her project will contribute to higher success rates in drug development: ‘By unravelling the importance of target binding kinetics, I am convinced that this project will provide a unique toolbox for future drug discovery. Moreover, it will drive a paradigm shift by rethinking the parameters used in the early drug discovery process.’