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SK4 K+ Channel Blockers: A New Treatment for Cardiac Arrhythmias
Ramot At Tel Aviv University
Small molecule
Cardiovascular disease
Hit To Lead or Lead Optimization
Unmet Needs
Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with significant mortality, due to embolic stroke and prevalence within ageing population. In the last decade, pulmonary vein ablation therapy was shown to have favorable anti-AF effects only in selected cases. Nevertheless, this approach is invasive, requires anticoagulants and is limited by cost, complexity, potential life threatening complications and incomplete efficacy because of recurrent AF attacks. Consequently, safe and effective pharmacological treatment options will remain the mainstay therapy for the estimated 30 million North Americans and Europeans that are expected to suffer from AF by 2050.
Our Solutions
SK4 K+ channels are important for the late repolarization of the action potential in the atrium and the pacemaker tissue (SAN, AV nodes). As such SK4 channel block will provide an increase in the atrial refractory period with a slowing of AV conduction.
Differentiation
Current available therapy for AF like catheter ablation raises questionable effectiveness, especially for patients with diabetes, obesity, hypertension, heart failure and for patients who cannot receive anticoagulant therapy. Several companies try to develop drugs against cardiac arrhythmias by targeting known ion channel targets (Nav, Kv, RyR, GAP junctions) but the pipeline body of new drugs is very thin and does not fill the gap of unmet need. Currently, our project is the sole to propose this new cardiac target: SK4 potassium channel blockers as a new therapy for Atrial Fibrillation. Thanks to their restricted expression, SK4 channels represent an ideal target for therapy.
Attali Bernard
PCT-IL2023-050048 (2023.01.17)
Patent Family: PCT
• "Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels". Weisbrod, D. et al. Acta Pharmacologica Sinica 2016, 37(1), 82–97
• "SK 4 K + channels are therapeutic targets for the treatment of cardiac arrhythmias". Haron-Khun, S. et al. Embo Molecular Medicine 2017, 9(4), 415–429
