Leveraging deep knowledge and experience, Ace Therapeutics is dedicated to supporting the development of highly effective and safe proton pump inhibitors (PPIs) to regulate gastric acid secretion and alleviate the burden of gastrointestinal (GI) diseases. Our drug development services start with computer-aided structural design of novel PPIs and cover the entire preclinical development process. We also provide customized animal models of GI diseases to support the pharmacological studies of our customers' PPIs, focusing on characteristics such as specificity, residence time and dose–response curve.
The Role of Proton Pumps in Gastrointestinal Diseases
The proton pump, also known as the H+/K+ ATPase, is a critical enzyme located in the parietal cells of the stomach lining that facilitates the exchange of hydrogen ions for potassium ions, leading to the secretion of gastric acid. This acidification process is essential for food digestion and pathogen defense. However, excessive or uncontrolled acid production can contribute to various gastrointestinal diseases, such as gastroesophageal reflux disease (GERD) and peptic ulcers. Proton pump inhibitors (PPIs) are a class of drugs that effectively target and inhibit this enzyme, reducing gastric acid secretion and providing therapeutic relief from these conditions.
Figure 1. The pathways of PPIs in inhibiting gastric acid secretion and their effects on gastric physiology. (Malfertheiner P., et al., 2017)
What Can We Do for the Development of Proton Pump Inhibitors?
- Effects of PPIs on Gastric Physiology
In Vitro Studies
In Vivo Studies
We utilize primary gastric cellsand cell lines to evaluate the effects of PPIs on gastric acid secretion.
- Measurement of gastric acid output: Employing techniques such as pH-stat titration and radiolabeled assays to quantify the inhibition of acid production by PPIs.
- Assessment of parietal cell function: Using immunofluorescence staining and Western blotting to assess the effects of PPIs on the expression and activity of proton pumps (H+/K+-ATPase) in parietal cells.
We utilize animal models of gastrointestinal diseases, such as peptic ulcer disease and GERD, to evaluate the effects of PPIs on gastric acid secretion and ulcer healing.
- Gastric pH monitoring: Using telemetric pH probes to continuously monitor gastric pH in animals treated with PPIs, providing insights into the duration and magnitude of acid suppression.
- Histopathological analysis: Performing histological analysis of gastric tissue to assess the effects of PPIs on gastric mucosal integrity, inflammation, and ulcer healing.
- Effects of PPIs on Gastric and Gut Microbiota
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| Antimicrobial Susceptibility Testing Against H. pylori |
- Perform susceptibility testing to determine the minimum inhibitory concentration (MIC) of PPIs against H. pylori.
- Investigate the molecular mechanisms by which PPIs affect H. pylori.
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| Gastric and Intestinal Microbiome Analysis |
Utilize next-generation sequencing and bioinformatics tools to analyze the composition and function of the gut microbiome in animals treated with PPIs. |
- Evaluation of Hepatotoxicity and Other Side Effects Caused by PPIs
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| Cytotoxicity Assays |
Conduct cytotoxicity assays to assess the effects of PPIs on cell viability and function. |
| Acute and Chronic Toxicity Studies |
Evaluate the potential for hepatotoxicity and other side effects, such as cardiovascular, renal, and neurovascular complications. |
| Drug Interactions of PPIs |
Assess the ability of PPIs to inhibit the activity of cytochrome P450 enzymes, which are involved in the metabolism of many drugs. |
At Ace Therapeutics, we offer a comprehensive suite of services for the development of proton pump inhibitors for the treatment of gastrointestinal diseases. Our research is thorough and multifaceted, focusing on key areas essential to the development of safe and effective PPIs. Please contact us to discuss how our expertise can be applied to your PPI programs.
Reference
- Malfertheiner P., et al. Proton-pump inhibitors: understanding the complications and risks. Nat Rev Gastroenterol Hepatol. 2017, 14(12):697-710.
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