3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide: Potent H+,K+-ATPase Inhibitor for Gastric Acid Research

Executive Summary: 3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide (SKU: A2845) is a highly selective H+,K+-ATPase inhibitor with an IC50 of 5.8 μM for enzyme inhibition and 0.16 μM for histamine-induced acid formation, providing robust suppression of gastric acid secretion (APExBIO, product page). The compound is supplied at ≥98% purity, verified by HPLC and NMR, and demonstrates superior solubility in DMSO (≥17.27 mg/mL) but is insoluble in water or ethanol. It is a solid at room temperature with a molecular weight of 345.42 and chemical formula C17H19N3O3S, and is stable at -20°C for long-term storage in solid form. These properties make it ideal for reproducible, sensitive antiulcer and gastric acid secretion research (see Optimizing Gastric Acid Secretion Research for protocol guidance). All usage is for scientific research only, not for diagnostic or medical purposes.

Biological Rationale

Gastric acid secretion is regulated by the H+,K+-ATPase (proton pump) in parietal cells. Dysregulated acid secretion underlies peptic ulcer disease and other gastric acid-related disorders. Inhibitors of the proton pump, such as 3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide, provide a controlled method to suppress acid secretion in cell and animal models. This enables analysis of pathophysiology and therapeutic interventions for ulcers, gastritis, and related diseases. Proton pump inhibitors also serve as reference agents for evaluating novel antiulcer compounds (APExBIO).

Mechanism of Action of 3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide

This compound acts as a potent, reversible inhibitor of the gastric H+,K+-ATPase enzyme. It binds to the ATPase catalytic site, blocking the exchange of hydrogen and potassium ions across the parietal cell membrane. This inhibition prevents proton secretion into the gastric lumen, thereby reducing acid output. The compound displays an IC50 of 5.8 μM for direct enzyme inhibition and 0.16 μM in histamine-stimulated acid formation assays (APExBIO). These values indicate strong potency in both biochemical and cell-based models. Structural features, such as the quinolinyl and trifluoromethoxyphenyl moieties, contribute to target selectivity and physicochemical stability.

Evidence & Benchmarks

• Demonstrates potent H+,K+-ATPase inhibition with an IC50 of 5.8 μM in enzyme assays (APExBIO).
• Suppresses histamine-induced gastric acid secretion with an IC50 of 0.16 μM in cell models (APExBIO).
• Supplied at ≥98% purity, as confirmed by HPLC and NMR analysis, ensuring reproducibility (APExBIO).
• Maintains solubility of ≥17.27 mg/mL in DMSO, supporting high-concentration stock solutions (see Optimizing Gastric Acid Research for solubility limits).
• Validated in multiple workflow scenarios for robust antiulcer and acid secretion research (Optimizing Gastric Acid Secretion Research).

Applications, Limits & Misconceptions

3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide is widely used in the following research settings:

• Modeling gastric acid-related disorders, including peptic ulcer disease, in cell and rodent models.
• Benchmarking new antiulcer agents against a well-characterized proton pump inhibitor.
• Studying mechanisms of H+,K+-ATPase inhibition and downstream signaling pathways.
• Optimizing cytotoxicity, proliferation, and viability assays in gastric cell lines (How 3-(quinolin-4-ylmethylamino)... Improves Assay Reproducibility extends these insights by providing troubleshooting strategies).

Common Pitfalls or Misconceptions

• Not water or ethanol soluble (use DMSO only for stock solutions).
• Not recommended for long-term storage in solution; always store as a solid at -20°C.
• For research use only; not approved for diagnostic or therapeutic administration to humans or animals.
• Effects are specific to H+,K+-ATPase; does not inhibit other ATPases at working concentrations.
• Assay conditions (pH, temperature, buffer) can influence inhibitor potency; standardize conditions for reproducibility (Scenario-Driven Solutions clarifies these methodologic boundaries).

Workflow Integration & Parameters

For optimal use, dissolve the solid compound in DMSO to make a concentrated stock (≥17.27 mg/mL). Dilute stocks freshly into assay buffer to avoid precipitation. Store all unused solid at -20°C in airtight containers. Do not freeze-thaw solutions repeatedly. For cell-based assays, use concentrations based on published IC50 values (0.16–5.8 μM) and always include vehicle controls. Validate each new lot’s purity using HPLC or NMR if possible. For detailed, scenario-driven protocols, see Optimizing Gastric Acid Secretion Research, which provides context-specific guidance on maximizing reproducibility and sensitivity, and Applied Use Cases, which details advanced troubleshooting and workflow optimization.

Conclusion & Outlook

3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide (APExBIO, SKU: A2845) is a validated, high-purity H+,K+-ATPase inhibitor for use in antiulcer and gastric acid secretion research. It combines robust potency, high stability, and reproducible assay performance under standardized conditions. While not suitable for therapeutic or diagnostic purposes, it remains a gold-standard research tool for elucidating proton pump pathways and benchmarking antiulcer activity. For further details and ordering, refer to the A2845 product page.