Mechanism of action: Acetylcholine-regulated inwardly rectifying potassium current (IKACh) blocker

Preclinical pharmacology

AZD2927 selectively blocks IKACh in human atrial myocytes (IC50=0.35µM) and in CHO cells expressing the human isoform of the channel protein (Kir3.1/Kir3.4, IC50=1.3µM) with minimal off-target activity. AZD2927 has limited CNS exposure in rats and so is thought to be restricted to the periphery. Efficacy was demonstrated in anaesthetised male NZW rabbit with AZD2927 producing a 20ms increase in the right atrial effective refractory period at a predicted unbound plasma concentration of 0.5µM. Similarly, in anaesthetised beagle dog a 20ms increase was observed at a predicted 0.2µM compound concentration. Antiarrhythmic efficacy was demonstrated in a dog disease model of rapid pacing-induced atrial fibrillation (AF) both in terms of restoring sinus rhythm and inhibiting induction of AF. AZD2927 was used as a tool compound for a Proof of Principle study in patients with atrial flutter but efficacy was not demonstrated at the dose tested.

Additional Information

Gene information from the NCBi

This compound works on the following genes: