BRET4CHANNEL

Ion channels are widely expressed in living cells and play critical roles in almost all physiological processes. However, they remain largely underexploited as important drug targets due to the inherent difficulties in studying them. Current methods, such as automated patch clamp, face limitations such as invasiveness and lack of throughput, despite ongoing improvements. Additionally, patch-clamp methods are ill-suited for addressing physicochemical constraints or studying ion channel while applying physical therapeutic means, such as electrical fields. To overcome these challenges, the BRET4CHANNEL project focuses on developing novel Bioluminescence Resonance Energy Transfer (BRET) probes. These probes enable non-invasive, real-time analysis of ion channels, even within intracellular organelles like lysosomes or mitochondria. This breakthrough facilitates easier and more cost-effective High-Throughput Screening (HTS) of drug candidates, driving advances in chemoinformatics to unravel the structure-function relationships of drugs targeting ion channels. By bridging scientific progress with technological applications, BRET4CHANNEL will identifies new classes of active molecules targeting ion channels, especially intracellular ones. It will refines the hit-to-lead process through in vitro, ex vivo, and in vivo studies, enhancing our understanding of ion channel activity in pathophysiological conditions. Moreover, BRET4CHANNEL will pave the way for non-invasive electroceutical therapies by gating ion channels using non-porating radiofrequency (RF) or ultra-short-pulsed electric field (usPEF) stimulation. Thanks to these approaches, BRET4CHANNEL will deliver therapeutic avenues for chemical and electroceutical therapies targeting ion channels involved in neuropathic and inflammatory pain, cancer proliferation, and arterial hypertension.