PF03716556-abs816320

PF-03716556 is a potent, and selective acid pump antagonist with pIC50 of 6.026, 6.038 and 6.009 at pH 6.4 for the inhibition of H+/K+-ATPase activity of porcine, canine and human ion-leaky membrane vesicles, respectively. PF-03716556 is used for the treatment of gastroesophageal reflux disease. PF-03716556 is highly selective for H+, K+-ATPase in vitro. PF-03716556 displays no activity at Na+, K+-ATPase. PF-03716556 inhibits gastric acid secretion in rat and dog models. PF-03716556 has no species differences among the porcine, canine and human enzymes. PF-03716556 produced greater inhibition than revaprazan in both the in vitro (ion-tight assay) and in vivo conditions. PF-03716556 offers long-lasting and maximal efficacy within 30 min of a single dosing with responses that are maintained for at least 5 days of repeated dosing with no signs of tolerance. PF-03716556 did not exhibit any biologically relevant activity against any of the tested more than 50 (e.g., adenosine receptor) receptors, ion channels, or enzymes expressed in naive tissues, cell lines and transfectants.