3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide: Precision 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 solid, high-purity H+,K+-ATPase inhibitor with an IC₅₀ of 5.8 μM, enabling precise inhibition of gastric acid secretion in vitro (APExBIO). The compound demonstrates antiulcer efficacy with a 0.16 μM IC₅₀ for histamine-induced acid formation (Ibid). Its molecular characteristics (C₁₇H₁₉N₃O₃S, MW 345.42) and DMSO solubility (≥17.27 mg/mL) support robust bench applications (ATP Solution Article). Purity is verified via HPLC and NMR, ensuring reproducibility. APExBIO supplies this compound for research use only, not for diagnostics or therapeutics.

Biological Rationale

Gastric acid secretion is regulated primarily by the H+,K+-ATPase enzyme, also known as the proton pump. Dysregulation of this pathway is implicated in peptic ulcer disease, gastroesophageal reflux, and other acid-related disorders. Inhibition of H+,K+-ATPase is the cornerstone of antiulcer pharmacology, allowing mechanistic and translational studies of acid suppression (Acridine Orange Review). 3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide offers a targeted approach for dissecting these mechanisms, with distinct advantages in potency and selectivity over older agents (Balaglitazone Protocols).

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

This compound acts as a direct inhibitor of the gastric H+,K+-ATPase, blocking proton translocation across the parietal cell membrane. The inhibition is concentration-dependent, with an in vitro IC₅₀ of 5.8 μM for the enzyme and a markedly lower IC₅₀ (0.16 μM) for histamine-induced acid formation, reflecting its high potency in cellular models (APExBIO). The molecular scaffold, featuring a quinolinyl moiety and a trifluoromethoxyphenyl group, confers enhanced affinity for the ATPase catalytic site. As a result, it is highly effective in models where proton pump inhibition is required for mechanistic or therapeutic investigation (Acridine Orange Review).

Evidence & Benchmarks

• Demonstrates in vitro H+,K+-ATPase inhibition with IC₅₀ = 5.8 μM (APExBIO, product page).
• Suppresses histamine-induced gastric acid secretion at IC₅₀ = 0.16 μM (APExBIO, product page).
• Molecular weight: 345.42; chemical formula: C₁₇H₁₉N₃O₃S; purity: ~98% by HPLC and NMR (APExBIO).
• Highly insoluble in water and ethanol; DMSO solubility ≥17.27 mg/mL (APExBIO, product page).
• Validated as a benchmark tool for antiulcer activity in gastric acid-related disorder models (ATP Solution).
• Recommended storage at -20°C; not intended for long-term solution storage (APExBIO, product page).

Applications, Limits & Misconceptions

3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide is used for:

• Inhibition of gastric acid secretion in vitro and ex vivo models (Balaglitazone Guide).
• Antiulcer activity studies in peptic ulcer disease models (CGS21680 Lab Guide).
• Proton pump inhibition pathway elucidation in molecular and signaling assays (ATP Luminescent Review).
• Research into the intersection of gastric acid regulation and neuroinflammatory models, as these pathways may intersect via the gut–brain axis (Xiang Kong et al., 2025).

Contrast: This article provides a consolidated, up-to-date benchmark summary integrating molecular data, storage parameters, and translational applications, extending prior discussions (ATP Solution) by emphasizing reproducibility and workflow integration.

Common Pitfalls or Misconceptions

• Not appropriate for diagnostic or human therapeutic use; for laboratory research only (APExBIO).
• Insoluble in aqueous buffers and ethanol; improper vehicle selection may hinder activity (APExBIO).
• Long-term storage in solution is discouraged due to stability loss; store as solid at -20°C (APExBIO).
• Does not model non-proton-pump mechanisms of acid secretion; selectivity must be considered in pathway analyses (Acridine Orange Review).

Workflow Integration & Parameters

The compound is supplied as a solid, ready for dissolution in DMSO at concentrations ≥17.27 mg/mL for in vitro use. All assays should be validated for DMSO concentrations to avoid solvent-related artifacts. For antiulcer or acid secretion studies, titrate concentrations between 0.1–10 μM to define dose–response curves. Purity is confirmed by HPLC and NMR, supporting robust experimental reproducibility (CGS21680 Guide). For stability, store at -20°C, and avoid repeated freeze–thaw cycles. Reference the A2845 kit for detailed handling instructions. This article updates earlier protocols (Balaglitazone Protocols) by clarifying precise solubility and storage parameters.

Conclusion & Outlook

3-(quinolin-4-ylmethylamino)-N-[4-(trifluoromethoxy)phenyl]thiophene-2-carboxamide, provided by APExBIO, is a well-validated, high-purity tool for research into gastric acid secretion and antiulcer mechanisms. Its robust inhibitory profile, reproducible purity, and solubility data make it suitable for advanced mechanistic studies and benchmarking in peptic ulcer disease models. Ongoing research into proton pump inhibition and its intersection with gut–brain axis signaling may further expand the compound’s utility (Xiang Kong et al., 2025). For up-to-date protocols and application notes, consult the product page.