NF 449 |
Catalog No.GC11326
One-Click Copy Product Info
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NF 449 is an efficient purine receptor antagonist, showing high selectivity for P2X1 (IC50 values for rP2X1, rP2X1+5, rP2X2+3, and rP2X3 receptors are 0.28, 0.69, 120, and 1820nM, respectively).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 627034-85-9
Sample solution is provided at 25 µL, 10mM.
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NF 449 is an efficient purine receptor antagonist, showing high selectivity for P2X1 (IC50 values for rP2X1, rP2X1+5, rP2X2+3, and rP2X3 receptors are 0.28, 0.69, 120, and 1820nM, respectively) [1]. NF 449 is a Gsα-selective G protein antagonist that inhibits the rate of GTP [γS] binding to Gsα-s, inhibits the stimulation of adenylate cyclase activity, and blocks the coupling of β-adrenergic receptors with Gs [2]. NF 449 can be used to distinguish the effects mediated by P2X1 and P2X7 in natural tissues [3].
In vitro, NF 449 (10μM; 5min) treatment significantly inhibited the activation of Gαs and cAMP production in GLP-1 (7-36) amide-treated muscle cells, and blocked the increase in PKA activity [4]. NF 449 (2μM; 10min) pretreatment of multi-cellular preparations of HGOA almost completely inhibited the contraction response caused by 10μM αβ-meATP, with the average normalized peak contraction amplitude changing from 100±12% to 6±2% [5].
In vivo, NF 449 (10, 50mg/kg/day; i.v.) single treatment inhibited the P2X1 receptor in systemic thromboembolic model WT mice and reduced intravascular platelet aggregation, but did not prolong the bleeding time. At higher doses, NF 449 inhibited ex vivo platelet aggregation, inhibited three types of platelet P2 receptors, and further reduced platelet consumption [6]. NF 449 (10mg/kg; twice; i.v.) treatment significantly reduced the protein content of BAL in LPS-sensitized H-2d BALB/c mice, and at the same time, the area of interstitial small artery periphery edema in the mice also decreased [7].
References:
[1] Rettinger J, et al. Profiling at recombinant homomeric and heteromeric rat P2X receptors identifies the suramin analogue NF 449 as a highly potent P2X1 receptor antagonist. Neuropharmacology. 2005;48(3):461-468.
[2] Hohenegger M, et al. Gsalpha-selective G protein antagonists. Proc Natl Acad Sci U S A. 1998;95(1):346-351.
[3] Hülsmann M, et al. NF 449, a novel picomolar potency antagonist at human P2X1 receptors. Eur J Pharmacol. 2003;470(1-2):1-7.
[4] May AT, et al. Identification of expression and function of the glucagon-like peptide-1 receptor in colonic smooth muscle. Peptides. 2019; 112:48-55.
[5] Nichols CM, et al. Vascular smooth muscle cells from small human omental arteries express P2X1 and P2X4 receptor subunits. Purinergic Signal. 2014;10(4):565-572.
[6] Hechler B, et al. Inhibition of platelet functions and thrombosis through selective or nonselective inhibition of the platelet P2 receptors with increasing doses of NF 449 [4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis-(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid octasodium salt]. J Pharmacol Exp Ther. 2005;314(1):232-243.
[7] El Mdawar M B, et al. The ATP-gated P2X1 ion channel contributes to the severity of antibody-mediated transfusion-related acute lung injury in mice[J]. Scientific Reports, 2019, 9(1): 5159.
| Cell experiment [1]: | |
Cell lines | ESCC cells |
Preparation Method | Muscle cells in culture were treated with GLP-1(7–36) amide (1μM) for 5min in the presence or absence of Gαs activation inhibitor, NF 449 (10μM). In some experiments, muscle cells were treated with 1μM vasoactive intestinal peptide (VIP) for 5min. Isobutyl methyl xanthine (IBMX, 100μM) was used in the incubation to prevent cAMP hydrolysis. At the end of 5-minute incubation, medium was removed. Carry out the activation assay of Gαs and the concentration determination of cAMP. |
Reaction Conditions | 10μM; 5min |
Applications | The treatment with NF 449 significantly inhibited the activation of Gαs and the production of cAMP in the muscle cells treated with GLP-1 (7-36) amide, and blocked the increase in PKA activity. |
| Animal experiment [2]: | |
Animal models | Wild-type mice |
Preparation Method | The experiment utilized an acute systemic vascular thromboembolic model triggered by an injection of a mixture of collagen and epinephrine. Briefly, male mice weighing 25 to 30g were anesthetized and the jugular veins were exposed surgically. NF 449 or physiological saline was injected into the left jugular vein, 30s before injecting a mixture of 0.1mg/kg collagen and 60g/kg adrenaline that was injected within an infusion time frame of 3 to 4s into the right jugular vein. Two minutes later, blood was drawn from the abdominal aorta into 6mM EDTA anticoagulant, and platelets were counted in an ACT Coulter DiffTM counter. |
Dosage form | 10, 50mg/kg/day; Single-dose; i.v. |
Applications | At a low dose, NF 449 inhibited the P2X1 receptor and reduced intravascular platelet aggregation, but did not prolong the bleeding time. At a higher dose, NF 449 inhibited platelet aggregation in vitro, and NF 449 inhibited three types of platelet P2 receptors, resulting in further reduction in platelet consumption. |
References: | |
| Cas No. | 627034-85-9 | SDF | |
| Chemical Name | sodium (1Z,3Z)-5-(((Z)-((3,5-bis((Z)-oxido((2-sulfo-4-sulfonatophenyl)imino)methyl)phenyl)imino)oxidomethyl)amino)-N'1-(2,4-disulfophenyl)-N'3-(2-sulfo-4-sulfonatophenyl)isophthalimidate | ||
| Canonical SMILES | [O-]/C(C1=CC(/C([O-])=N/C2=C(S(O)(=O)=O)C=C(S([O-])(=O)=O)C=C2)=CC(/N=C([O-])/NC3=CC(/C([O-])=N/C4=C(S(O)(=O)=O)C=C(S([O-])(=O)=O)C=C4)=CC(/C([O-])=N/C5=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C=C5)=C3)=C1)=N\C6=C(S(O)(=O)=O)C=C(S([O-])(=O)=O)C=C6.[Na+].[Na+].[Na+].[ | ||
| Formula | C41H24N6Na8O29S8 | M.Wt | 1505.06 |
| Solubility | PBS (pH 7.2): 10 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 664.4 μL | 3.3221 mL | 6.6443 mL |
| 5 mM | 132.9 μL | 664.4 μL | 1.3289 mL |
| 10 mM | 66.4 μL | 332.2 μL | 664.4 μL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 19 reference(s) in Google Scholar.)