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MedKoo Cat#: 525978 | Name: PHA-543613
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PHA-543613 acts as a potent and selective agonist for the α7 subtype of neural nicotinic acetylcholine receptors, with a high level of brain penetration and good oral bioavailability. It is under development as a possible treatment for cognitive deficits in schizophrenia.

Chemical Structure

PHA-543613
PHA-543613
CAS#478149-53-0

Theoretical Analysis

MedKoo Cat#: 525978

Name: PHA-543613

CAS#: 478149-53-0

Chemical Formula: C15H17N3O2

Exact Mass: 271.1321

Molecular Weight: 271.32

Elemental Analysis: C, 66.40; H, 6.32; N, 15.49; O, 11.79

Price and Availability

Size Price Availability Quantity
5mg USD 325.00 2 Weeks
25mg USD 850.00 2 Weeks
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Related CAS #
478148-58-2 (2HCl) 1586767-92-1 (HCl) 478149-53-0
Synonym
PHA-543613; PHA 543613; PHA543613.
IUPAC/Chemical Name
(R)-N-(Quinuclidin-3-yl)furo(2,3-C)pyridine-5-carboxamide
InChi Key
IPKZCLGGYKRDES-ZDUSSCGKSA-N
InChi Code
InChI=1S/C15H17N3O2/c19-15(12-7-11-3-6-20-14(11)8-16-12)17-13-9-18-4-1-10(13)2-5-18/h3,6-8,10,13H,1-2,4-5,9H2,(H,17,19)/t13-/m0/s1
SMILES Code
O=C(C1=CC2=C(OC=C2)C=N1)N[C@H]3CN4CCC3CC4
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PHA-543613 is a potent, orally active, brain-penetrant and selective α7 nAChR agonist with a Ki of 8.8 nM.
In vitro activity:
To identity the target cells of the α7nAChR agonist PHA-543613, this study used murine dermal fibroblasts (MDF). In WT MDF (murine dermal fibroblasts), PHA-543613 suppressed ECM gene expression induced by TGF-β1. Gene silencing of α7nAChR by small interfering RNA neutralized the effects of PHA-543613 on TGF-β1-mediated ECM gene expression. Reference: Neuroendocrinology. 2022;112(5):446-456. https://pubmed.ncbi.nlm.nih.gov/34120115/
In vivo activity:
Male CD-1 mice (n=109) were subjected to intracerebral infusion of autologous blood (n=88) or sham surgery (n=21). ICH animals received vehicle administration, 4 or 12 mg/kg of α7nAChR agonist PHA-543613, 12 mg/kg of α7nAChR agonist PNU-282987, 6 mg/kg of α7nAChR antagonist methyllycaconitine (MLA), 15 μg/kg of phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, or PHA-543613 combined with MLA or wortmannin. α7nAChR stimulation improved neurological outcome and reduced brain edema at 24 and 72 hours after surgery (P<0.05 compared with vehicle). Furthermore, PHA-543613 treatment increased p-Akt and decreased p-GSK-3β and CC3 expressions in the ipsilateral hemisphere (P<0.05, respectively), which was reversed by MLA and wortmannin. P-Akt, p-GSK-3β, and CC3 were generally localized in neurons. PHA-543613 reduced neuronal cell death in the perihematomal area (P<0.05). Reference: Stroke. 2012 Mar;43(3):844-50. https://pubmed.ncbi.nlm.nih.gov/22207510/
Solvent mg/mL mM comments
Solubility
Water 100.0 368.57
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 271.32 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Stegemann A, Raker V, Del Rey A, Steinbrink K, Böhm M. Expression of the α7 Nicotinic Acetylcholine Receptor Is Critically Required for the Antifibrotic Effect of PHA-543613 on Skin Fibrosis. Neuroendocrinology. 2022;112(5):446-456. doi: 10.1159/000517772. Epub 2021 Jun 11. PMID: 34120115. 2. Ji L, Chen Y, Wei H, Feng H, Chang R, Yu D, Wang X, Gong X, Zhang M. Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia. Brain Res. 2019 Jul 15;1715:57-65. doi: 10.1016/j.brainres.2019.03.016. Epub 2019 Mar 18. PMID: 30898676. 1. Lv J, Duan Y, Wang X, Wu H, Chen J, Zhang W, Ke S, Wang F, Ni H, Cao X. Alpha7 nicotinic acetylcholine receptor agonist PHA-543613 improves memory deficits in presenilin 3 and presenilin 2 conditional double knockout mice. Exp Neurol. 2023 Jan;359:114271. doi: 10.1016/j.expneurol.2022.114271. Epub 2022 Nov 10. PMID: 36370840. 4. Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH. α7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3β inhibition in a mouse model of intracerebral hemorrhage. Stroke. 2012 Mar;43(3):844-50. doi: 10.1161/STROKEAHA.111.639989. Epub 2011 Dec 29. PMID: 22207510; PMCID: PMC3293395.
In vitro protocol:
1. Stegemann A, Raker V, Del Rey A, Steinbrink K, Böhm M. Expression of the α7 Nicotinic Acetylcholine Receptor Is Critically Required for the Antifibrotic Effect of PHA-543613 on Skin Fibrosis. Neuroendocrinology. 2022;112(5):446-456. doi: 10.1159/000517772. Epub 2021 Jun 11. PMID: 34120115. 2. Ji L, Chen Y, Wei H, Feng H, Chang R, Yu D, Wang X, Gong X, Zhang M. Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia. Brain Res. 2019 Jul 15;1715:57-65. doi: 10.1016/j.brainres.2019.03.016. Epub 2019 Mar 18. PMID: 30898676.
In vivo protocol:
1. Lv J, Duan Y, Wang X, Wu H, Chen J, Zhang W, Ke S, Wang F, Ni H, Cao X. Alpha7 nicotinic acetylcholine receptor agonist PHA-543613 improves memory deficits in presenilin 1 and presenilin 2 conditional double knockout mice. Exp Neurol. 2023 Jan;359:114271. doi: 10.1016/j.expneurol.2022.114271. Epub 2022 Nov 10. PMID: 36370840. 2. Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH. α7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3β inhibition in a mouse model of intracerebral hemorrhage. Stroke. 2012 Mar;43(3):844-50. doi: 10.1161/STROKEAHA.111.639989. Epub 2011 Dec 29. PMID: 22207510; PMCID: PMC3293395.
1: Sadigh-Eteghad S, Mahmoudi J, Babri S, Talebi M. Effect of alpha-7 nicotinic acetylcholine receptor activation on beta-amyloid induced recognition memory impairment. Possible role of neurovascular function. Acta Cir Bras. 2015 Nov;30(11):736-42. doi: 10.1590/S0102-865020150110000003. PubMed PMID: 26647792. 2: Sérrière S, Doméné A, Vercouillie J, Mothes C, Bodard S, Rodrigues N, Guilloteau D, Routier S, Page G, Chalon S. Assessment of the Protection of Dopaminergic Neurons by an α7 Nicotinic Receptor Agonist, PHA 543613 Using [(18)F]LBT-999 in a Parkinson's Disease Rat Model. Front Med (Lausanne). 2015 Sep 2;2:61. doi: 10.3389/fmed.2015.00061. eCollection 2015. PubMed PMID: 26389120; PubMed Central PMCID: PMC4556971. 3: Zhang W, Liu Y, Hou B, Gu X, Ma Z. Activation of spinal alpha-7 nicotinic acetylcholine receptor attenuates remifentanil-induced postoperative hyperalgesia. Int J Clin Exp Med. 2015 Feb 15;8(2):1871-9. eCollection 2015. PubMed PMID: 25932115; PubMed Central PMCID: PMC4402762. 4: Sadigh-Eteghad S, Talebi M, Mahmoudi J, Babri S, Shanehbandi D. Selective activation of α7 nicotinic acetylcholine receptor by PHA-543613 improves Aβ25-35-mediated cognitive deficits in mice. Neuroscience. 2015 Jul 9;298:81-93. doi: 10.1016/j.neuroscience.2015.04.017. Epub 2015 Apr 13. PubMed PMID: 25881725. 5: Garcia-Oscos F, Peña D, Housini M, Cheng D, Lopez D, Cuevas-Olguin R, Saderi N, Salgado Delgado R, Galindo Charles L, Salgado Burgos H, Rose-John S, Flores G, Kilgard MP, Atzori M. Activation of the anti-inflammatory reflex blocks lipopolysaccharide-induced decrease in synaptic inhibition in the temporal cortex of the rat. J Neurosci Res. 2015 Jun;93(6):859-65. doi: 10.1002/jnr.23550. Epub 2015 Jan 27. PubMed PMID: 25626997. 6: Bali ZK, Inkeller J, Csurgyók R, Bruszt N, Horváth H, Hernádi I. Differential effects of α7 nicotinic receptor agonist PHA-543613 on spatial memory performance of rats in two distinct pharmacological dementia models. Behav Brain Res. 2015 Feb 1;278:404-10. doi: 10.1016/j.bbr.2014.10.030. Epub 2014 Oct 30. PubMed PMID: 25447295. 7: Macpherson A, Zoheir N, Awang RA, Culshaw S, Ramage G, Lappin DF, Nile CJ. The alpha 7 nicotinic receptor agonist PHA-543613 hydrochloride inhibits Porphyromonas gingivalis-induced expression of interleukin-8 by oral keratinocytes. Inflamm Res. 2014 Jul;63(7):557-68. doi: 10.1007/s00011-014-0725-5. Epub 2014 Mar 8. PubMed PMID: 24609617; PubMed Central PMCID: PMC4050294. 8: Gannon RL, Garcia DA, Millan MJ. Effects of systemically applied nAChRα7 agonists and antagonists on light-induced phase shifts of hamster circadian activity rhythms. Eur Neuropsychopharmacol. 2014 Jun;24(6):964-73. doi: 10.1016/j.euroneuro.2013.12.007. Epub 2013 Dec 17. PubMed PMID: 24388152. 9: Mazloom R, Eftekhari G, Rahimi-Balaei M, Khori V, Hajizadeh S, Dehpour AR, Mani AR. The role of α7 nicotinic acetylcholine receptor in modulation of heart rate dynamics in endotoxemic rats. PLoS One. 2013 Dec 10;8(12):e82251. doi: 10.1371/journal.pone.0082251. eCollection 2013. Erratum in: PLoS One. 2013;8(12). doi:10.1371/annotation/4103a8bf-a523-4db9-91f2-d974b175aafa. PLoS One. 2015;10(5):e0127826. Rahimi, Maryam [corrected to Rahimi-Balaei, Maryam]. PubMed PMID: 24340009; PubMed Central PMCID: PMC3858293. 10: Harenza JL, Muldoon PP, De Biasi M, Damaj MI, Miles MF. Genetic variation within the Chrna7 gene modulates nicotine reward-like phenotypes in mice. Genes Brain Behav. 2014 Feb;13(2):213-25. doi: 10.1111/gbb.12113. Epub 2013 Dec 26. PubMed PMID: 24289814; PubMed Central PMCID: PMC3919514. 11: Salamone A, Mura E, Zappettini S, Grilli M, Olivero G, Preda S, Govoni S, Marchi M. Inhibitory effects of beta-amyloid on the nicotinic receptors which stimulate glutamate release in rat hippocampus: the glial contribution. Eur J Pharmacol. 2014 Jan 15;723:314-21. doi: 10.1016/j.ejphar.2013.11.011. Epub 2013 Nov 23. PubMed PMID: 24275353. 12: Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M. Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):12078-83. doi: 10.1073/pnas.1307849110. Epub 2013 Jul 1. PubMed PMID: 23818597; PubMed Central PMCID: PMC3718126. 13: Krafft PR, Caner B, Klebe D, Rolland WB, Tang J, Zhang JH. PHA-543613 preserves blood-brain barrier integrity after intracerebral hemorrhage in mice. Stroke. 2013 Jun;44(6):1743-7. doi: 10.1161/STROKEAHA.111.000427. Epub 2013 Apr 23. PubMed PMID: 23613493; PubMed Central PMCID: PMC3696522. 14: Freitas K, Ghosh S, Ivy Carroll F, Lichtman AH, Imad Damaj M. Effects of α7 positive allosteric modulators in murine inflammatory and chronic neuropathic pain models. Neuropharmacology. 2013 Feb;65:156-64. doi: 10.1016/j.neuropharm.2012.08.022. Epub 2012 Oct 16. PubMed PMID: 23079470; PubMed Central PMCID: PMC3521074. 15: Freitas K, Negus SS, Carroll FI, Damaj MI. In vivo pharmacological interactions between a type II positive allosteric modulator of α7 nicotinic ACh receptors and nicotinic agonists in a murine tonic pain model. Br J Pharmacol. 2013 Jun;169(3):567-79. doi: 10.1111/j.1476-5381.2012.02226.x. PubMed PMID: 23004024; PubMed Central PMCID: PMC3682705. 16: Kita Y, Ago Y, Takano E, Fukada A, Takuma K, Matsuda T. Galantamine increases hippocampal insulin-like growth factor 2 expression via α7 nicotinic acetylcholine receptors in mice. Psychopharmacology (Berl). 2013 Feb;225(3):543-51. doi: 10.1007/s00213-012-2841-7. Epub 2012 Aug 30. PubMed PMID: 22932776. 17: Gao Y, Ravert HT, Valentine H, Scheffel U, Finley P, Wong DF, Dannals RF, Horti AG. 5-(5-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)pyridin-2-yl)-1H-indole as a potential PET radioligand for imaging cerebral α7-nAChR in mice. Bioorg Med Chem. 2012 Jun 15;20(12):3698-702. doi: 10.1016/j.bmc.2012.04.056. Epub 2012 May 4. PubMed PMID: 22608919; PubMed Central PMCID: PMC3527104. 18: Wang Q, Wang F, Li X, Yang Q, Li X, Xu N, Huang Y, Zhang Q, Gou X, Chen S, Xiong L. Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats. J Neuroinflammation. 2012 Jan 26;9:24. doi: 10.1186/1742-2094-9-24. PubMed PMID: 22277256; PubMed Central PMCID: PMC3297509. 19: Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH. α7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3β inhibition in a mouse model of intracerebral hemorrhage. Stroke. 2012 Mar;43(3):844-50. doi: 10.1161/STROKEAHA.111.639989. Epub 2011 Dec 29. PubMed PMID: 22207510; PubMed Central PMCID: PMC3293395. 20: Zappettini S, Mura E, Grilli M, Preda S, Salamone A, Olivero G, Govoni S, Marchi M. Different presynaptic nicotinic receptor subtypes modulate in vivo and in vitro the release of glycine in the rat hippocampus. Neurochem Int. 2011 Oct;59(5):729-38. doi: 10.1016/j.neuint.2011.06.022. Epub 2011 Jul 5. PubMed PMID: 21762741.