PNU 282987 |
| Catalog No.GC12952 |
PNU 282987 is a selective α7 nicotinic acetylcholine receptor (α7nAChR) agonist associated with an anti-inflammatory pathway as well as an antagonist of the 5-HT3 receptor, the EC50 of PNU 282987 for α7nAChR is 154nM (Ki α7nAChR=27nM, rat brain homogenates) while IC50 for 5-HT3 receptor is 4541nM (Ki 5-HT3R=1662nM, GR-65630).
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Cas No.: 123464-89-1
Sample solution is provided at 25 µL, 10mM.
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PNU 282987 is a selective α7 nicotinic acetylcholine receptor (α7nAChR) agonist associated with an anti-inflammatory pathway as well as an antagonist of the 5-HT3 receptor, the EC50 of PNU 282987 for α7nAChR is 154nM (Ki α7nAChR=27nM, rat brain homogenates) while IC50 for 5-HT3 receptor is 4541nM (Ki 5-HT3R=1662nM, GR-65630) [1][2]. α7nAChR agonists can restore the anti-inflammatory function in the brain by activating α7nAChR and competing against α7 nAChR inhibitors such as amyloid beta at the orthosteric binding site of α7nAChR[3]. 5-HT3 receptor (5-HT3R) antagonist blocks afferent and efferent synaptic transmission by blocking fast depolarizing response mediated by Na+, K+, and Ca2+, however, the binding site of PNU 282987 at 5-HT3 receptor is not well-identified[4].
in vitro experiments show that PNU 282987(5μM, 30min treatment) reduce TNF-α release in full-length human α7nAChR-expressing mouse fibroblast NIH3T3 treated with lipopolysaccharid[5]. PNU 282987(3μM, 7min treatment) triggers a robust concentration-dependent increase in ERK1/2 phosphorylation in PC12 cells pretreated with p38 inhibitors[6]. PNU 282987(5 and 50μM, 48h treated) also attenuated BCAA-induced injury in primary murine cardiomyocytes[7].
In vivo experiments show that PNU 282987(3mg/kg, once, i.p) has protective effects on intestinal epithelial barrier dysfunction in LPS-induced endotoxemic rats[8]. PNU 282987 (2mg/ml, once, 40min recovery, i.p) is able to reverse scopolamine-induced memory impairment and restore it back to normal levels[9].
References:
[1]. Pohanka, Miroslav. “Alpha7 nicotinic acetylcholine receptor is a target in pharmacology and toxicology.” *International journal of molecular sciences* vol. 13,2 (2012): 2219-2238. doi:10.3390/ijms13022219.
[2]. Bodnar, Alice L et al. “Discovery and structure-activity relationship of quinuclidine benzamides as agonists of alpha7 nicotinic acetylcholine receptors.” *Journal of medicinal chemistry* vol. 48,4 (2005): 905-8. doi:10.1021/jm049363q
[3]. Cecon, Erika et al. “Quantitative assessment of oligomeric amyloid β peptide binding to α7 nicotinic receptor.” *British journal of pharmacology* vol. 176,18 (2019): 3475-3488. doi:10.1111/bph.14688
[4]. Machu, Tina K. “Therapeutics of 5-HT3 receptor antagonists: current uses and future directions.” *Pharmacology & therapeutics* vol. 130,3 (2011): 338-47. doi:10.1016/j.pharmthera.2011.02.003.
[5]. Li, Dong-Jie et al. “Overexpressed alpha7 nicotinic acetylcholine receptor inhibited proinflammatory cytokine release in NIH3T3 cells.” *Journal of bioscience and bioengineering* vol. 108,2 (2009): 85-91. doi:10.1016/j.jbiosc.2009.03.004.
[6]. Gubbins, Earl J et al. “Alpha7 nAChR-mediated activation of MAP kinase pathways in PC12 cells.” *Brain research* vol. 1328 (2010): 1-11. doi:10.1016/j.brainres.2010.02.083.
[7]. Jiang, Yu-Jie et al. “Excessive ROS production and enhanced autophagy contribute to myocardial injury induced by branched-chain amino acids: Roles for the AMPK-ULK1 signaling pathway and α7nAChR.” *Biochimica et biophysica acta. Molecular basis of disease* vol. 1867,1 (2021): 165980. doi:10.1016/j.bbadis.2020.165980.
[8]. Zhang, Ying et al. “PNU-282987 Attenuates Intestinal Epithelial Barrier Dysfunction in LPS-Induced Endotoxemia.” *Inflammation* vol. 43,2 (2020): 417-424. doi:10.1007/s10753-019-01096-w.
[9]. Pandya, Anshul A, and Jerrel L Yakel. “Activation of the α7 nicotinic ACh receptor induces anxiogenic effects in rats which is blocked by a 5-HT₁a receptor antagonist.” *Neuropharmacology* vol. 70 (2013): 35-42. doi:10.1016/j.neuropharm.2013.01.004.
| Cell experiment [1]: | |
Cell lines | RAW264.7, MOVAS |
Preparation Method | The cells were plated on 60-mm culture dishes at a density of 2×105 cells/ml, permitted to adhere in complete medium for 24h, and changed to serum-free medium (RAW264.7 cells) or 1 % serum medium (MOVAS cells) to serum starve the cells overnight. The next day, the medium was changed and the cells were pretreated with PNU 282987 for 30min prior to being supplemented with an appropriate concentration of nicotine. After the cells were exposed to nicotine for 3h, both the supernatant and cells were harvested. |
Reaction Conditions | 0.1, 1, 10, and 100µM for 30min |
Applications | Cells were pretreated with PNU 282987 (α7nAChR agonist) prior to nicotine exposure, the nicotine-induced upregulation of VCAM-1, MMP-2, MMP-9, and p-JNK was suppressed, with a joint treatment producing a more significant inhibitory effect. Moreover, PNU 282987 had a comparable inhibitory effect on VCAM-1, MMP-2, and MMP-9 expressions and JNK activation via phosphorylation. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6 mice |
Preparation Method | Based on salt weight and concentration, compounds were dissolved in 0.9% saline, the injection volume is 1ml/kg body weight, followed by daily doses at 24h intervals. Control animals were injected with saline. |
Dosage form | 1mg/kg/day, 21 days maximum, i.p |
Applications | PNU 282987 reduced inflammatory factors (MCP-1, IL-1β, MMP-9, TNF-α, HMGB1, TLR2), promoted the polarization of macrophage/microglia into anti-inflammatory subtypes(CD206), repaired blood-brain barrier injury (ZO-1, Claudin-5, Occludin), alleviated acute brain edema and then recovered neurological dysfunction. |
References: | |
| Cas No. | 123464-89-1 | SDF | |
| Chemical Name | 4-chloro-N-((1S,3R,4S)-quinuclidin-3-yl)benzamide | ||
| Canonical SMILES | ClC1=CC=C(C=C1)C(N[C@@H]2[C@H](CC3)CC[N@]3C2)=O | ||
| Formula | C14H17ClN2O | M.Wt | 264.75 |
| Solubility | DMF: 10 mg/ml,DMSO: 30 mg/ml,Ethanol: 20 mg/ml,PBS (pH 7.2): 5 mg/ml | Storage | 4°C, sealed storage, away from moisture. |
| 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. |
||
| 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 | 3.7771 mL | 18.8857 mL | 37.7715 mL |
| 5 mM | 0.7554 mL | 3.7771 mL | 7.5543 mL |
| 10 mM | 0.3777 mL | 1.8886 mL | 3.7771 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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 ddH2O, 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.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 25 reference(s) in Google Scholar.)
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