Soraprazan: setting new standards in inhibition of gastric acid secretion.

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Simon WA, Herrmann M, Klein T, Shin JM, Huber R, Senn-Bilfinger J, Postius S

Soraprazan: setting new standards in inhibition of gastric acid secretion.

J Pharmacol Exp Ther. 2007 Jun;321(3):866-74. Epub 2007 Mar 16.

PubMed ID

17369284 [ View in PubMed

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Abstract

After treatment of millions of patients suffering from gastroesophageal reflux disease (GERD) and other acid-related ailments with proton pump inhibitors, there are still unmet medical needs such as rapid and reliable pain relief, especially for nocturnal acid breakthrough. In this work, we introduce and characterize the biochemistry and pharmacology of the potassium-competitive acid blocker (P-CAB) soraprazan, a novel, reversible, and fast-acting inhibitor of gastric H,K-ATPase. Inhibitory and binding properties of soraprazan were analyzed together with its mode of action, its selectivity, and its in vivo potency. This P-CAB has an IC(50) of 0.1 microM if measured with ion leaky vesicles and of 0.19 microM in isolated gastric glands. With a K(i) of 6.4 nM, a K(d) of 26.4 nM, and a B(max) of 2.89 nmol/mg, this compound is a highly potent and reversible inhibitor of the H,K-ATPase. Soraprazan shows immediate inhibition of acid secretion in various in vitro models and in vivo and was found to be more than 2000-fold selective for H,K-ATPase over Na,K- and Ca-ATPases. Soraprazan is superior to esomeprazole in terms of onset of action and the extent and duration of pH elevation in vivo in the dog. Rapid and consistent inhibition of acid secretion by soraprazan renders the P-CABs a promising group of compounds for therapy of GERD.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Potassium acetate	Sodium/potassium-transporting ATPase subunit alpha-1	Protein	Humans	Unknown	Not Available	Details
Potassium cation	Sodium/potassium-transporting ATPase subunit alpha-1	Protein	Humans	Unknown	Not Available	Details
Potassium sulfate	Sodium/potassium-transporting ATPase subunit alpha-1	Protein	Humans	Unknown	Not Available	Details