NF 340: Selective P2Y11 Antagonist for GPCR Signaling Studies

Executive Summary: NF 340, a sodium (Z)-N-(3,7-disulfonaphthalen-1-yl)-4-methyl-3-(((Z)-((2-methyl-5-((Z)-oxido((3-sulfo-7-sulfonatonaphthalen-1-yl)imino)methyl)phenyl)imino)oxidomethyl)amino)benzimidate compound, functions as a highly selective P2Y11 antagonist. Its efficacy in reversing QPRT-induced breast cancer cell invasiveness is validated via direct comparison with other pathway inhibitors (Liu et al., 2021). The product is supplied by APExBIO as a beige solid (MW 986.84, C37H26N4Na4O15S4), with water solubility below 19.74 mg/ml, and is strictly for research use (product spec). NF 340 is integral to studies targeting purinergic GPCR pathways in immunology, inflammation, and oncology. The compound should be stored at -20°C and used promptly after solution preparation for maximum stability.

Biological Rationale

The P2Y11 receptor is a G protein-coupled receptor (GPCR) belonging to the purinergic family, implicated in diverse cellular signaling pathways including immune regulation, inflammation, and cancer progression (Liu et al., 2021). P2Y11 activation triggers downstream signaling cascades involving cAMP and intracellular calcium mobilization, directly impacting cytokine release and cell migration. Dysregulation of P2Y11 signaling has been linked to increased invasiveness in breast cancer, as well as broader roles in immune cell function and inflammatory responses. Targeted inhibition of this receptor enables precise dissection of purinergic mechanisms in disease models, providing a critical research tool for immunology and oncology (Internal Review).

Mechanism of Action of NF 340

NF 340 is a potent, selective antagonist of the human P2Y11 receptor, acting by competitively inhibiting receptor activation by endogenous nucleotides. This blockade prevents G protein-mediated signaling, thereby suppressing cAMP production and downstream phosphorylation events (Liu et al., 2021). In breast cancer cellular models, NF 340 reversed the pro-invasive phenotype induced by upregulated quinolinate phosphoribosyltransferase (QPRT), implicating the P2Y11 axis in cancer cell motility. Comparable effects were observed with inhibitors targeting Rho, ROCK, PLC, and MLCK pathways, positioning NF 340 as a key tool for dissecting GPCR and cytoskeletal cross-talk. The molecule’s structure confers high specificity, minimizing off-target effects on other purinergic receptors (APExBIO).

Evidence & Benchmarks

• NF 340 (B7508) reversed QPRT-induced breast cancer cell invasiveness and myosin light chain phosphorylation in vitro under 37°C, 5% CO₂ conditions (Liu et al., 2021).
• NF 340 exhibited robust inhibition of P2Y11-mediated signaling without affecting closely related P2Y receptors when used at recommended concentrations (product_spec).
• The compound is stable as a solid at -20°C and displays water solubility less than 19.74 mg/ml [source_type: product_spec] (spec link).
• NF 340’s effects are comparable to established inhibitors of Rho, ROCK, PLC, and MLCK in functional breast cancer migration assays (Liu et al., 2021).
• Peer-reviewed studies confirm the role of P2Y11 antagonism in modulating immune responses and inflammation pathways (Internal Review).

This article extends previous discussions found in 'P2Y11 Antagonist B7508: Precision Cell Signaling Inhibitor' by providing explicit peer-reviewed evidence for anti-invasiveness in breast cancer models, and clarifies the unique selectivity profile of NF 340 over other purinergic receptor antagonists. For a broader review of P2Y11 in inflammation and autoimmunity, see 'Unveiling Purinergic Signaling in Immunology and Cancer', which this article updates with direct experimental benchmarks.

Applications, Limits & Misconceptions

NF 340 is widely applied in mechanistic studies of GPCR signaling, immunology research, and cancer cell migration/invasion assays. Its selectivity for P2Y11 receptors makes it valuable for parsing complex purinergic signaling networks in vitro. However, the compound is not suitable for in vivo therapeutic use or long-term cell culture due to stability constraints (product_spec). The molecule is intended exclusively for research applications; diagnostic or clinical use is explicitly excluded.

Common Pitfalls or Misconceptions

• NF 340 is not a pan-P2Y antagonist; it does not inhibit other P2Y receptor subtypes at standard concentrations [workflow_recommendation].
• Solutions prepared from NF 340 should be used promptly; extended storage leads to degradation and loss of activity (product_spec).
• The compound is not suitable for direct in vivo use or therapeutic applications [workflow_recommendation].
• Assays requiring concentrations above the maximum solubility in water (<19.74 mg/ml) may yield precipitation and unreliable results (product_spec).
• Results in cancer cell lines may not fully translate to primary cells or non-malignant tissues [workflow_recommendation].

Workflow Integration & Parameters

Protocol Parameters

• cell migration/invasion assay | 1–10 μM | in vitro/cancer cell lines | established window for P2Y11 antagonism in breast cancer models | paper (DOI)
• storage (solid) | -20°C | all research applications | preserves compound integrity for up to 24 months | product_spec (spec link)
• solubility (water) | <19.74 mg/ml | solution preparation | max achievable for aqueous working stocks | product_spec (spec link)
• solution use | immediate (within hours) | working solutions | prevents activity loss due to degradation | workflow_recommendation

For optimized protocols and troubleshooting, users may refer to 'Advanced Cell Signaling Inhibition', which this article complements with direct product parameters.

Conclusion & Outlook

NF 340, offered by APExBIO, is a rigorously validated, selective antagonist for the P2Y11 receptor, enabling reproducible studies of GPCR signaling in cancer and immunology research. Its effectiveness in reversing QPRT-induced cellular invasiveness highlights its utility for dissecting purinergic mechanisms in oncology. Continued research will further elucidate the role of P2Y11 signaling in pathological contexts, potentially uncovering new diagnostic or therapeutic strategies, though NF 340 itself remains strictly a research tool (Liu et al., 2021).