PHA 568487 free base

• CAT Number: I011680
• CAS Number: 527680-56-4
• Molecular Formula: C16H20N2O3
• Molecular Weight: 288.34
• Purity: ≥95%
• Synonyms: N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-2,3-dihydro-1,4-benzodioxine-6-carboxamide
• InChI: 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
• InChIKey: LUVXHMJTVXZFPD-ZDUSSCGKSA-N
• SMILES: C1CN2CCC1C(C2)NC(=O)C3=CC4=C(C=C3)OCCO4

PHA 568487 free base is a selective alpha 7 nicotinic acetylcholine receptor (α-7 nAchR) agonist. PHA 568487 free base reduces neuroinflammation[1][2][3].
PHA 568487, α-7 nAchR-specific agonist, prevents NF-κb activation in the cells[2].
PHA 568487 treatment significantly reduces the expression of leukocyte infiltration molecules in MCAO rats and in endothelial cells after in vitro ischemia[3].
PHA 568487 treatment reduces mouse cognitive decline caused by aseptic bone fracture by promoting inflammation resolution. PHA 568487 (PHA; 0.8 mg/kg; injected intraperitoneally) reduces infarct volume and TUNEL positive neurons in the peri-infarct regions of permanent middle cerebral artery occlusion (pMCAO) and pMCAO+tibia fracture mice[2].
The role played by a7 receptors on neuroinflammation is supported by the decrease of [18F]DPA-714 binding in ischemic rats treated with the a7 agonist PHA 568487 at day 7 after MCAO[3].
PHA 568487-treated ischemic rats show a significant reduction of the cerebral infarct volumes and an improvement of the neurologic outcome compared with non-treated MCAO rats[3].

Reference

[1]. F Barclay Shilliday, et al. Multiple species metabolism of PHA-568487, a selective alpha 7 nicotinic acetylcholine receptor agonist. Drug Metab Lett. 2010 Aug;4(3):162-72.
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[2]. Zhenying Han, et al. Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture. J Neurochem. 2014 Nov;131(4):498-508.
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[3]. Lorena Colás, et al. In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia. Glia. 2018 Aug;66(8):1611-1624.
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