Next generation anti-epileptic drugs: Indentification of chemical starting points for the discovery of novel GluK negative allosteric modifications (360G-Wellcome-109702_Z_15_Z)

Epilepsy is a chronic neurological condition characterised by recurrent, unprovoked seizures. It is the 41h most common neurological disorder estimated to affect -50 million patients globally. Despite a variety of anti-epileptic drugs (AEDs) in clinical use, -30% of patients are not effectively managed by current therapies and are termed 'intractable' or 'refractory' epilepsy patients. Additionally current AEDs exhibit significant side effects resulting in early treatment discontinuation in up to 1 in 4 patients. This award will fund Professors Martin Gosling, John Atack and Simon Ward in the Drug Discovery Centre at the University of Sussex to identify chemical starting points for the development of novel AEDs. These molecules, which will negatively modulate kainate (GiuK) receptor subtypes, would represent a novel class of pharmacological agents for utility as AEDs with the potential to deliver benefit in refractory patients by virtue of their differentiated pharmacological mechanism. Additionally the optimisation of both the selectivity and CNS exposure profiles is expected to equate to reduced side effects and improved tolerability. The group will use Pathfinder funding to undertake a combination of screening and structural approaches to identify candidate lead structures.