A novel, potent, and selective acid pump antagonist for the treatment of gastroesophageal reflux disease.
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.
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].
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].
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.
[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.
