New drugs targeting the cardiac ultra-rapid delayed-rectifier current (I Kur): 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 patents published since 1993); however, to realize the full value of this therapeutic drug target, 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.
Ford
John W
JW
Xention Ltd, Iconix park, Cambridge, UK. john.ford@xention.com
Milnes
James T
JT
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers