NF 340: Selective P2Y11 Antagonist for GPCR Signaling Research

Executive Summary: NF 340 is a highly selective antagonist of the P2Y11 receptor, a G protein-coupled receptor involved in critical immune and inflammation pathways (APExBIO product page). It inhibits P2Y11-mediated signaling, directly modulating downstream cellular processes relevant for autoimmune, cancer, and neuroinflammatory research (Liu et al., 2021). NF 340 demonstrates low water solubility (<19.74 mg/ml) and should be stored at -20°C for optimal stability (APExBIO). Its efficacy in reversing QPRT-induced breast cancer cell invasiveness highlights its value as a precision tool for dissecting purinergic signaling in disease models. The compound is intended exclusively for research use and is not suitable for diagnostic or therapeutic applications (APExBIO).

Biological Rationale

The P2Y11 receptor is a member of the purinergic receptor family, classified as a G protein-coupled receptor (GPCR). It is activated by extracellular nucleotides, such as ATP, and regulates cellular signaling in immune, inflammatory, and apoptotic pathways (Liu et al., 2021). Dysregulation of P2Y11 signaling has been implicated in immune system disorders, inflammatory diseases, and cancer progression. The need for selective chemical tools to dissect these pathways has driven the development and adoption of antagonists like NF 340 for advanced research applications.

Mechanism of Action of NF 340

NF 340 acts as a selective P2Y11 antagonist by competitively inhibiting the binding of endogenous ligands (e.g., ATP) to the P2Y11 receptor. This inhibition prevents activation of downstream G protein signaling cascades, including the PLC-IP3-Ca²⁺ pathway and Rho/ROCK-mediated cytoskeletal changes. In breast cancer cellular models, NF 340 reversed QPRT-driven invasiveness and myosin light chain phosphorylation, confirming its ability to block purinergic signaling at the receptor level (Liu et al., 2021).

Evidence & Benchmarks

• NF 340 (SKU: B7508) selectively inhibits P2Y11 receptor activity in human cell lines, with minimal off-target effects on other P2Y subtypes (APExBIO).
• In MDA-MB-231 breast cancer cells, NF 340 reversed quinolinate phosphoribosyltransferase (QPRT)-induced cell migration and invasion (Liu et al., 2021).
• NF 340 treatment reduced phosphorylation of myosin light chain, a downstream target of the Rho/ROCK pathway, in QPRT-overexpressing cancer cells (Liu et al., 2021).
• NF 340 is a beige solid, molecular weight 986.84, with water solubility less than 19.74 mg/ml; optimal storage is at -20°C (APExBIO).
• NF 340 is for research use only and not approved for diagnostic or therapeutic purposes (APExBIO).

This article extends prior coverage, such as 'P2Y11 Antagonist: Precision Tool for GPCR Signaling Research', by providing recent peer-reviewed evidence on NF 340's efficacy in cancer models and highlighting its biochemical parameters for reproducible workflows. It also updates the protocol guidance detailed in 'Optimizing Cell Signaling Assays with P2Y11 Antagonist (SKU B7508)' by incorporating newly published findings on QPRT and pathway specificity.

Applications, Limits & Misconceptions

NF 340 is employed in studies of GPCR signaling, purinergic pathway modulation, immune response, inflammation, apoptosis, and cancer metastasis. Its selectivity and rapid action make it valuable for dissecting the mechanistic roles of the P2Y11 receptor in both physiological and pathological contexts.

Common Pitfalls or Misconceptions

• NF 340 does not inhibit P2Y receptors other than P2Y11 at recommended concentrations—cross-reactivity is negligible (APExBIO).
• This compound is not suitable for in vivo diagnostic or therapeutic use; it is strictly for in vitro or ex vivo research (APExBIO).
• Long-term storage of NF 340 solutions is not advised; degradation may occur, reducing potency (APExBIO).
• NF 340's low water solubility (<19.74 mg/ml) may necessitate the use of co-solvents or optimized buffers for some applications.
• It should not be used as a generic GPCR antagonist; efficacy is specific to P2Y11.

Workflow Integration & Parameters

For optimal experimental outcomes, NF 340 (APExBIO, SKU B7508) should be dissolved in DMSO or appropriate buffer at concentrations up to its solubility limit. Solutions must be freshly prepared and used promptly. Storage at -20°C is recommended for the solid form. Concentrations used in published studies typically range from 1 to 10 μM in cell culture assays (Liu et al., 2021).

When integrating NF 340 into workflows, it is important to use validated controls and reference inhibitors, such as Y16 (Rho inhibitor) and Y27632 (ROCK inhibitor), for pathway specificity. Guidance from 'P2Y11 Antagonist: Precision Tool for GPCR Signaling Modulation' can aid in troubleshooting and experimental design, but this article provides updated storage and solubility parameters for NF 340.

Conclusion & Outlook

NF 340 is a robust, highly selective inhibitor of the P2Y11 receptor, enabling targeted investigation of purinergic and GPCR-mediated signaling in immunology, inflammation, and cancer research. Its validated efficacy in reversing QPRT-induced cell invasiveness and pathway activation underscores its utility in advanced mechanistic studies. For full product details or to order, refer to the NF 340 product page. As ongoing research elucidates new roles for P2Y11 signaling, NF 340 will remain a critical tool for precision pathway modulation and hypothesis-driven discovery.