New drugs targeting the cardiac ultra-rapid delayed-rectifier Current(IKur):: Rationale, pharmacology and evidence for potential therapeutic value

There is a clear unmet medical need for new pharmacologic therapies for the treatment of atrial fibrillation (AF) with improved efficacy and safety. This article reviews the development of new and novel Kv1.5/ultra-rapid delayed-rectifier current (I-Kur) inhibitors and presents evidence that Kv1.5 modulation provides an atrial-selective mechanism for treating AF Academia and industry have invested heavily in Kv1.5 (> 500 scientific publications and > 50 patients published since 1993); however, to realize the full value of this therapeutic drug clinical efficacy and safety data are required for a selective Kv1.5 modulator. The reward for demonstrating clinical efficacy and safety in a pivotal Phase 3 trial, on regulatory approval, is "first in class" status.