| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
PHA 568487 targets the alpha-7 nicotinic acetylcholine receptor (α7 nAChR). It is a highly selective agonist with a Ki of 44 nM for α7 nAChR compared to 2800 nM for 5-HT3. It is heavily utilized as a benchmark compound in neuroinflammation, ischemic stroke, and cognitive deficit models due to its optimized metabolic stability and high receptor selectivity.
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| ln Vitro |
A α-7 nAchR-specific agonist, PHA 568487, inhibits NF-κb activation in cells[2]. Following in vitro ischemia, PHA 568487 treatment dramatically lowers the expression of leukocyte infiltration molecules in MCAO rats and endothelial cells[3].
In vitro, PHA 568487 acts as a selective α7 nAChR agonist. It prevents NF-kB activation in cells. Its activity is typically assessed by measuring its ability to activate α7 nAChR-mediated signaling pathways. The compound shows high selectivity for α7 nAChR over other receptors, with a Ki of 44 nM for α7 compared to 2800 nM for 5-HT3. Standard in vitro assays include receptor binding studies and functional assays measuring calcium influx or downstream signaling. |
| ln Vivo |
Through the promotion of inflammation resolution, PHA 568487 therapy mitigates the cognitive deterioration in mice resulting from aseptic bone fractures. Intraperitoneally administered PHA 568487 (PHA; 0.8 mg/kg) decreases TUNEL positive neurons and infarct volume in the peri-infarct areas of permanent middle cerebral artery occlusion (pMCAO) and pMCAO+tibia fracture mice[2]. The decrease of [18F]DPA-714 binding in ischemic rats treated with the a7 agonist PHA 568487 at day 7 after MCAO[3] provides evidence for the role a7 receptors play in neuroinflammation. When compared to non-treated MCAO rats, ischemic rats treated with PHA 568487 exhibit a significant reduction in cerebral infarct volumes and an improvement in the neurologic outcome[3].
In vivo, PHA 568487 is a brain-penetrant compound. It has been studied for its potential to attenuate neuroinflammation. It is used in models of neuroinflammation, ischemic stroke, and cognitive deficits. The free base form offers flexibility in formulation for in vitro and in vivo studies. However, comprehensive in vivo efficacy data from published literature are limited. |
| Enzyme Assay |
For non-cell-based receptor binding assays, PHA 568487 can be evaluated using membrane preparations from cells expressing human α7 nAChRs. Radioligand binding displacement experiments are performed using a suitable radiolabeled ligand such as [3H]-methyllycaconitine or [125I]-α-bungarotoxin. Membrane homogenates are incubated with increasing concentrations of the test compound and a fixed concentration of the radioligand. Bound radioligand is separated from free by rapid filtration through glass fiber filters. Non-specific binding is determined in the presence of excess unlabeled α-bungarotoxin. Ki values are calculated from displacement curves using nonlinear regression analysis.
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| Cell Assay |
For in vitro cellular assays, cells expressing human α7 nAChRs are cultured in appropriate media. For functional assays, calcium influx is measured using fluorescent calcium indicators such as Fluo-4 AM. Cells are loaded with the dye and treated with various concentrations of PHA 568487. Fluorescence intensity is measured using a fluorescence plate reader. The increase in calcium signal compared to control wells indicates agonist activity. EC50 values are calculated from dose-response curves. For signaling assays, the activation of downstream pathways such as NF-kB can be assessed.
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| Animal Protocol |
Animal/Disease Models: C57BL/6J male mice (10-12 weeks old) with pMCAO[2]
Doses: 0.4 and 0.8 mg/kg Route of Administration: Injected intraperitoneally (ip) once on day 1, or twice on days 1 and 2, after pMCAO Experimental Results: 0.8 mg/kg on days 1 and 2 after pMCAO yielded the best effect on infarct volume and behavior tests. Animal/Disease Models: Adult male SD (Sprague-Dawley) rats[3] Doses: 1.25 mg/kg Route of Administration: Treated ip daily with 0.1 mL Experimental Results: demonstrated a significant decrease of [18F]DPA-714 binding in the ischemic cerebral hemisphere in comparison to non-treated ischemic rats. For in vivo animal studies, PHA 568487 can be administered to rodents via intraperitoneal or intravenous injection. In models of neuroinflammation, its effects on inflammatory markers and neuronal damage are assessed. In models of ischemic stroke, its neuroprotective effects are evaluated. In models of cognitive deficits, behavioral tests are performed. Dosing regimens vary depending on the specific model and desired exposure levels. |
| ADME/Pharmacokinetics |
PHA 568487 free base has a molecular weight of 288.34 g/mol and a molecular formula of C16H20N2O3. The free base form is specifically selected over the more common fumarate salt when researchers require custom non-aqueous formulations, lipid-based delivery systems, or need to avoid the local pH shifts associated with acidic counterions. It is for research use only and is not intended for human consumption.
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| Toxicity/Toxicokinetics |
The toxicity profile of PHA 568487 has not been extensively reported. As an α7 nAChR agonist, potential adverse effects may include modulation of cholinergic signaling. The compound is for research use only and is not intended for human consumption. Standard safety precautions should be observed when handling the compound.
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| References |
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| Additional Infomation |
PHA 568487 free base (CAS 527680-56-4) is a highly selective, brain-penetrant agonist of the alpha-7 nicotinic acetylcholine receptor (α7 nAChR). It is an azabicyclic aryl amide compound specifically optimized to mitigate bioactivation liabilities. It is used as a benchmark compound in neuroinflammation, ischemic stroke, and cognitive deficit models. It is available for research purposes only.
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| Molecular Formula |
C16H20N2O3
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| Molecular Weight |
288.34
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| Exact Mass |
404.158
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| CAS # |
527680-56-4
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| Related CAS # |
PHA 568487;527680-57-5
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| PubChem CID |
9932000
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| Appearance |
White to off-white solid powder
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| LogP |
1.322
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
395
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CN2CCC1[C@H](C2)NC(=O)C3=CC4=C(C=C3)OCCO4
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| InChi Key |
LUVXHMJTVXZFPD-ZDUSSCGKSA-N
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| InChi Code |
InChI=1S/C16H20N2O3/c19-16(17-13-10-18-5-3-11(13)4-6-18)12-1-2-14-15(9-12)21-8-7-20-14/h1-2,9,11,13H,3-8,10H2,(H,17,19)/t13-/m0/s1
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| Chemical Name |
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-2,3-dihydro-1,4-benzodioxine-6-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 25 mg/mL (86.70 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4681 mL | 17.3406 mL | 34.6813 mL | |
| 5 mM | 0.6936 mL | 3.4681 mL | 6.9363 mL | |
| 10 mM | 0.3468 mL | 1.7341 mL | 3.4681 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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