The potassium-transporting ATPase alpha chain 1 (ATP4A) is the catalytic subunit of the ATP4A:ATP4B heteromer and is the enzyme required for the final step in the secretion of gastric acid. Potassium-transporting ATPase inhibitors, commonly referred to as a proton pump inhibitor drugs (PPI) are used in the treatment of gastroesophageal reflux disease (GERD) (Badillo & Francis 2014), peptic ulcer diseases (Malik et al. 2021), dyspepsia (Pinto-Sanchez et al. 2017), and Zollinger–Ellison syndrome (Cho & Kasi 2020). PPIs suppress stomach acid secretion by specific inhibition of ATP4A found at the secretory surface of gastric parietal cells (review - SAchs et al. 2006).

All currently approved PPIs are benzimidazole derivatives; heterocyclic compounds that include both a pyridine and benzimidazole moiety linked by a methylsulfinyl group. The prototypical example is omeprazole. Omeprazole was the first clinical PPI. It is a racemate (can exist as either the (S)- or (R)-enantiomers). Both enantiomers can be converted to achiral products (sulfenic acid and sulfenamide) which react with a cysteine group in ATP4A, thereby inhibiting the ability of the parietal cells to produce gastric acid (Lind et al. 1983). Other PPIs that function in the same way include esomeprazole, lansoprazole, rabeprazole and dexlansoprazole (Strand et al. 2017). Ilaprazole is still under clinical trials in the US but studies show that ilaprazole is at least as potent a PPI as omeprazole when taken in equivalent doses (Wang et al. 2016).

The novel imidazopyridine PPIs, tenatoprazole and tenatoprazole have prolonged half-lives over their benzimidazole relatives which may confer improved acid control overnight (Sach et al. 2006). Tenatoprazole is undergoing clinical evaluation (Hunt et al. 2010, Li et al. 2013).