IC50: In porcine ion-tight membrane vesicles, PF-03716556 inhibited H+,K+-ATPase activity in a concentration-dependent manner, with a pIC50 value of 7.095 ± 0.077 at pH 7.4.
The gastric H+,K+-ATPase, which is responsible for gastric acid secretion, is a P2-type ATPase located in the apical membrane of parietal cells. Inhibition of the H+,K+-ATPase is currently the most effective way to control gastric acid secretion and remains an attractive target for the medical treatment of acidrelated diseases. PF-03716556 is a novel, potent, and selective acid pump antagonist for the treatment of gastroesophageal reflux disease.
In vitro: PF-03716556 demonstrated 3-fold greater inhibitory activity than revaprazan, the only acid pump antagonist that has been available on the market, in ion-tight assay. Kinetics experiments revealed that PF-03716556 has a competitive and reversible mode of action [1].
In vivo: PF-03716556 did not display any species differences, exhibiting highly selective profile including the canine kidney H+,K+-ATPase. In addition, more rapid onset of action than omeprazole and 3-fold greater potency than revaprazan were observed in Ghosh-Schild rats and Heidenhain pouch dogs [2].
Clinical trials: Currenlty no clinical data are available.
Reference:
[1] Mori H, Tonai-Kachi H, Ochi Y, Taniguchi Y, Ohshiro H, Takahashi N, Aihara T, Hirao A, Kato T, Sakakibara M, Kurebayashi Y. N-(2-hydroxyethyl)-N,2-dimethyl-8-{[(4R)-5-methyl-3,4- dihydro-2H-chromen-4-yl]amino}imidazo[1,2-a]pyridine-6-carboxamide (PF-03716556), a novel, potent, and selective acid pump antagonist for the treatment of gastroesophageal reflux disease. J Pharmacol Exp Ther. 2009;328(2):671-9.