Proton pump inhibitors (PPIs) are widely used in the treatment of acid-related diseases such as gastroesophageal reflux disease; however, rapid symptom relief and suppression of night time acid secretion remain unmet medical needs. Another class of acid blockers is the potassium-competitive acid blockers (P-CABs), Hori et al. describe the discovery of new, potent, and long acting P-CAB, TAK-438 [1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate]. Unlike lansoprazole, a typical PPI, or SCH28080 [3-(cyanomethyl)-2-methyl,8-(phenylmethoxy)imidazo(1,2-a)pyridine], an early-generation P-CAB, TAK-438, was unaffected by ambient pH, reversible like SCH28080, more potent in vivo, and completely inhibited basal and stimulated gastric acid secretion in rats, and its effect was sustained longer than either agent in vivo. Given that TAK-438 is a pyrrole derivative with a chemical structure that is completely different from other P-CABs developed to date along with superior properties to other P-CABs, TAK-438 has the potential to have improved efficacy and avoid hepatotoxicity observed with predecessor P-CABs. TAK-438 may provide a new option for patients whose acid-related disease is refractory or inadequately controlled by PPIs.
See article at J Pharmacol Exp Ther 2010, 335:231–238.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics