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MedKoo Cat#: 526804 | Name: PNU-120596
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Description:

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

PNU-120596, also known as NSC 216666, is α7 nicotinic acetylcholine receptor positive allosteric modulator. PNU-120596 reverses a sub-chronic phencyclidine-induced cognitive deficit in the attentional set-shifting task in female rats. PNU-120596 augments the effects of donepezil on learning and memory in aged rodents and non-human primates.

Chemical Structure

PNU-120596
PNU-120596
CAS#501925-31-1

Theoretical Analysis

MedKoo Cat#: 526804

Name: PNU-120596

CAS#: 501925-31-1

Chemical Formula: C13H14ClN3O4

Exact Mass: 311.0673

Molecular Weight: 311.72

Elemental Analysis: C, 50.09; H, 4.53; Cl, 11.37; N, 13.48; O, 20.53

Price and Availability

Size Price Availability Quantity
10mg USD 400.00 2 Weeks
25mg USD 650.00 2 Weeks
50mg USD 875.00 2 Weeks
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No Data
Synonym
PNU-120596; PNU 120596; PNU120596; NSC 216666; NSC-216666; NSC216666.
IUPAC/Chemical Name
1-(5-Chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea
InChi Key
CEIIEALEIHQDBX-UHFFFAOYSA-N
InChi Code
InChI=1S/C13H14ClN3O4/c1-7-4-12(17-21-7)16-13(18)15-9-5-8(14)10(19-2)6-11(9)20-3/h4-6H,1-3H3,(H2,15,16,17,18)
SMILES Code
O=C(NC1=NOC(C)=C1)NC2=CC(Cl)=C(OC)C=C2OC
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:
PNU-120596 (NSC 216666) is a potent and selective α7 nAChR positive allosteric modulator (PMA) with an EC50 of 216 nM.
In vitro activity:
PNU-120596 caused changes in cysteine accessibility at the inner beta sheet, transition zone, and agonist binding site. These changes in accessibility are similar to but not identical to those caused by ACh alone. In particular, PNU-120596 induced changes in MTSEA accessibility at N170C (in the transition zone) that were substantially different from those evoked by acetylcholine (ACh). This study found that PNU-120596 induced changes at position E172C in the absence of allosteric modulation. This study identified a cysteine mutation of the agonist binding site (W148C) that exhibited an unexpected phenotype in which PNU-120596 acts as a full agonist. Reference: Mol Pharmacol. 2009 Aug;76(2):253-63. https://pubmed.ncbi.nlm.nih.gov/19411608/
In vivo activity:
In in vivo experiments, both pre- and post-ischaemia treatments with PNU-120596 (30 mg·kg(-1) , s.c. and 1 mg·kg(-1) , i.v., respectively) significantly reduced the cortical/subcortical infarct volume caused by transient focal cerebral ischaemia. PNU-120596 (1 mg·kg(-1) , i.v., 30 min post-ischaemia) remained neuroprotective in rats subjected to a choline-deficient diet for 14 days prior to experiments. Reference: Br J Pharmacol. 2013 Aug;169(8):1862-78. https://pubmed.ncbi.nlm.nih.gov/23713819/
Solvent mg/mL mM
Solubility
DMF 30.0 96.24
DMF:PBS (pH 7.2) (1:1) 0.5 1.60
DMSO 33.7 108.18
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 311.72 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. Barron SC, McLaughlin JT, See JA, Richards VL, Rosenberg RL. An allosteric modulator of alpha7 nicotinic receptors, N-(5-Chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea (PNU-120596), causes conformational changes in the extracellular ligand binding domain similar to those caused by acetylcholine. Mol Pharmacol. 2009 Aug;76(2):253-63. doi: 10.1124/mol.109.056226. Epub 2009 May 1. PMID: 19411608; PMCID: PMC2713121. 2. Hurst RS, Hajós M, Raggenbass M, Wall TM, Higdon NR, Lawson JA, Rutherford-Root KL, Berkenpas MB, Hoffmann WE, Piotrowski DW, Groppi VE, Allaman G, Ogier R, Bertrand S, Bertrand D, Arneric SP. A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci. 2005 Apr 27;25(17):4396-405. doi: 10.1523/JNEUROSCI.5269-04.2005. PMID: 15858066; PMCID: PMC6725110. 3. Gowayed MA, El-Sayed NS, Matar NA, Afify EA, El-Ganainy SO. The α7 nAChR allosteric modulator PNU-120596 amends neuroinflammatory and motor consequences of parkinsonism in rats: Role of JAK2/NF-κB/GSk3β/ TNF-α pathway. Biomed Pharmacother. 2022 Apr;148:112776. doi: 10.1016/j.biopha.2022.112776. Epub 2022 Mar 7. PMID: 35272136. 4. Kalappa BI, Sun F, Johnson SR, Jin K, Uteshev VV. A positive allosteric modulator of α7 nAChRs augments neuroprotective effects of endogenous nicotinic agonists in cerebral ischaemia. Br J Pharmacol. 2013 Aug;169(8):1862-78. doi: 10.1111/bph.12247. PMID: 23713819; PMCID: PMC3753841.
In vitro protocol:
1. Barron SC, McLaughlin JT, See JA, Richards VL, Rosenberg RL. An allosteric modulator of alpha7 nicotinic receptors, N-(5-Chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea (PNU-120596), causes conformational changes in the extracellular ligand binding domain similar to those caused by acetylcholine. Mol Pharmacol. 2009 Aug;76(2):253-63. doi: 10.1124/mol.109.056226. Epub 2009 May 1. PMID: 19411608; PMCID: PMC2713121. 2. Hurst RS, Hajós M, Raggenbass M, Wall TM, Higdon NR, Lawson JA, Rutherford-Root KL, Berkenpas MB, Hoffmann WE, Piotrowski DW, Groppi VE, Allaman G, Ogier R, Bertrand S, Bertrand D, Arneric SP. A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci. 2005 Apr 27;25(17):4396-405. doi: 10.1523/JNEUROSCI.5269-04.2005. PMID: 15858066; PMCID: PMC6725110.
In vivo protocol:
1. Gowayed MA, El-Sayed NS, Matar NA, Afify EA, El-Ganainy SO. The α7 nAChR allosteric modulator PNU-120596 amends neuroinflammatory and motor consequences of parkinsonism in rats: Role of JAK2/NF-κB/GSk3β/ TNF-α pathway. Biomed Pharmacother. 2022 Apr;148:112776. doi: 10.1016/j.biopha.2022.112776. Epub 2022 Mar 7. PMID: 35272136. 2. Kalappa BI, Sun F, Johnson SR, Jin K, Uteshev VV. A positive allosteric modulator of α7 nAChRs augments neuroprotective effects of endogenous nicotinic agonists in cerebral ischaemia. Br J Pharmacol. 2013 Aug;169(8):1862-78. doi: 10.1111/bph.12247. PMID: 23713819; PMCID: PMC3753841.
1: Mukhtasimova N, Bouzat C, Sine SM. Novel interplay between agonist and calcium binding sites modulates drug potentiation of α7 acetylcholine receptor. Cell Mol Life Sci. 2024 Aug 7;81(1):332. doi: 10.1007/s00018-024-05374-1. PMID: 39110172; PMCID: PMC11335256. 2: Neves JLB, Urcino C, Chase K, Dowell C, Hone AJ, Morgenstern D, Chua VM, Ramiro IBL, Imperial JS, Leavitt LS, Phan J, Fisher FA, Watkins M, Raghuraman S, Tun JO, Ueberheide BM, McIntosh JM, Vasconcelos V, Olivera BM, Gajewiak J. Using Constellation Pharmacology to Characterize a Novel α-Conotoxin from Conus ateralbus. Mar Drugs. 2024 Feb 29;22(3):118. doi: 10.3390/md22030118. PMID: 38535458; PMCID: PMC10971446. 3: Acker BA, Badescu VO, Berkenpas MB, Groppi VE, Hajós M, Higdon NR, Hurst RS, Jon Jacobsen E, Margolis BJ, McWhorter WW, Myers JK, Piotrowski DW, Rogers BN, Sarapa D, Vetman TN, Walker DP, Wall TM, Wilhite DM, Wishka DG, Xu W, Yates KM. Positive allosteric modulators of the α7 nicotinic acetylcholine receptor: SAR investigation around PNU-120596. Bioorg Med Chem Lett. 2023 Sep 1;93:129433. doi: 10.1016/j.bmcl.2023.129433. Epub 2023 Aug 7. PMID: 37557923. 4: Rodd ZA, Swartzwelder HS, Waeiss RA, Soloviov SO, Lahiri DK, Engleman EA, Truitt WA, Bell RL, Hauser SR. Negative and positive allosteric modulators of the α7 nicotinic acetylcholine receptor regulates the ability of adolescent binge alcohol exposure to enhance adult alcohol consumption. Front Behav Neurosci. 2023 Apr 4;16:954319. doi: 10.3389/fnbeh.2022.954319. PMID: 37082421; PMCID: PMC10113115. 5: Papke RL, Quadri M, Gulsevin A. Silent agonists for α7 nicotinic acetylcholine receptors. Pharmacol Res. 2023 Apr;190:106736. doi: 10.1016/j.phrs.2023.106736. Epub 2023 Mar 20. PMID: 36940890. 6: Gzielo K, Nikiforuk A. The Effects of Positive Allosteric Modulators of α7-nAChR on Social Play Behavior in Adolescent Rats Prenatally Exposed to Valproic Acid. Pharmaceuticals (Basel). 2022 Nov 16;15(11):1417. doi: 10.3390/ph15111417. PMID: 36422547; PMCID: PMC9697996. 7: Stokes C, Camacho-Hernandez GA, Thakur GA, Wu X, Taylor P, Papke RL. Differential Activation and Desensitization States Promoted by Noncanonical α7 Nicotinic Acetylcholine Receptor Agonists. J Pharmacol Exp Ther. 2022 Nov;383(2):157-171. doi: 10.1124/jpet.122.001354. Epub 2022 Sep 2. PMID: 36279397; PMCID: PMC9553115. 8: Zhuang Y, Noviello CM, Hibbs RE, Howard RJ, Lindahl E. Differential interactions of resting, activated, and desensitized states of the α7 nicotinic acetylcholine receptor with lipidic modulators. Proc Natl Acad Sci U S A. 2022 Oct 25;119(43):e2208081119. doi: 10.1073/pnas.2208081119. Epub 2022 Oct 17. PMID: 36251999; PMCID: PMC9618078. 9: Papke RL, Karaffa M, Horenstein NA, Stokes C. Coffee and cigarettes: Modulation of high and low sensitivity α4β2 nicotinic acetylcholine receptors by n-MP, a biomarker of coffee consumption. Neuropharmacology. 2022 Sep 15;216:109173. doi: 10.1016/j.neuropharm.2022.109173. Epub 2022 Jun 27. PMID: 35772522; PMCID: PMC9524580. 10: Belanger-Coast MG, Zhang M, Bugay V, Gutierrez RA, Gregory SR, Yu W, Brenner R. Dequalinium chloride is an antagonists of α7 nicotinic acetylcholine receptors. Eur J Pharmacol. 2022 Jun 15;925:175000. doi: 10.1016/j.ejphar.2022.175000. Epub 2022 May 4. PMID: 35525312. 11: Gowayed MA, El-Sayed NS, Matar NA, Afify EA, El-Ganainy SO. The α7 nAChR allosteric modulator PNU-120596 amends neuroinflammatory and motor consequences of parkinsonism in rats: Role of JAK2/NF-κB/GSk3β/ TNF-α pathway. Biomed Pharmacother. 2022 Apr;148:112776. doi: 10.1016/j.biopha.2022.112776. Epub 2022 Mar 7. PMID: 35272136. 12: Wang H, Li Y, Yang M, Zhou M. Synthesis and characterization of αM-conotoxin SIIID, a reversible human α7 nicotinic acetylcholine receptor antagonist. Toxicon. 2022 Apr 30;210:141-147. doi: 10.1016/j.toxicon.2022.03.002. Epub 2022 Mar 4. PMID: 35255330. 13: Gil de Biedma-Elduayen L, Giménez-Gómez P, Morales-Puerto N, Vidal R, Núñez- de la Calle C, Gutiérrez-López MD, O'Shea E, Colado MI. Influx of kynurenine into the brain is involved in the reduction of ethanol consumption induced by Ro 61-8048 after chronic intermittent ethanol in mice. Br J Pharmacol. 2022 Jul;179(14):3711-3726. doi: 10.1111/bph.15825. Epub 2022 Mar 7. PMID: 35189673; PMCID: PMC9314579. 14: Jin XT, Drenan RM. Functional α7 nicotinic acetylcholine receptors in GABAergic neurons of the interpeduncular nucleus. Neuropharmacology. 2022 May 1;208:108987. doi: 10.1016/j.neuropharm.2022.108987. Epub 2022 Feb 12. PMID: 35167902; PMCID: PMC8885883. 15: Gulsevin A, Papke RL, Stokes C, Tran HNT, Jin AH, Vetter I, Meiler J. The Allosteric Activation of α7 nAChR by α-Conotoxin MrIC Is Modified by Mutations at the Vestibular Site. Toxins (Basel). 2021 Aug 10;13(8):555. doi: 10.3390/toxins13080555. PMID: 34437426; PMCID: PMC8402416. 16: Targowska-Duda KM, Budzynska B, Michalak A, Wnorowski A, Loland CJ, Maj M, Manetti D, Romanelli MN, Jozwiak K, Biala G, Arias HR. Type I and type II positive allosteric modulators of α7 nicotinic acetylcholine receptors induce antidepressant-like activity in mice by a mechanism involving receptor potentiation but not neurotransmitter reuptake inhibition. Correlation with mTOR intracellular pathway activation. Eur Neuropsychopharmacol. 2021 Nov;52:31-47. doi: 10.1016/j.euroneuro.2021.06.006. Epub 2021 Jul 6. PMID: 34237657. 17: Pismataro MC, Horenstein NA, Stokes C, Dallanoce C, Thakur GA, Papke RL. Stable desensitization of α7 nicotinic acetylcholine receptors by NS6740 requires interaction with S36 in the orthosteric agonist binding site. Eur J Pharmacol. 2021 Aug 15;905:174179. doi: 10.1016/j.ejphar.2021.174179. Epub 2021 May 15. PMID: 34004208; PMCID: PMC8478151. 18: Morales JY, Young-Stubbs CM, Shimoura CG, Kem WR, Uteshev VV, Mathis KW. Systemic Administration of α7-Nicotinic Acetylcholine Receptor Ligands Does Not Improve Renal Injury or Behavior in Mice With Advanced Systemic Lupus Erythematosus. Front Med (Lausanne). 2021 Apr 13;8:642960. doi: 10.3389/fmed.2021.642960. PMID: 33928103; PMCID: PMC8076522. 19: Loser D, Hinojosa MG, Blum J, Schaefer J, Brüll M, Johansson Y, Suciu I, Grillberger K, Danker T, Möller C, Gardner I, Ecker GF, Bennekou SH, Forsby A, Kraushaar U, Leist M. Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons. Arch Toxicol. 2021 Jun;95(6):2081-2107. doi: 10.1007/s00204-021-03031-1. Epub 2021 Mar 29. PMID: 33778899; PMCID: PMC8166715. 20: Gaidhani N, Tucci FC, Kem WR, Beaton G, Uteshev VV. Therapeutic efficacy of α7 ligands after acute ischaemic stroke is linked to conductive states of α7 nicotinic ACh receptors. Br J Pharmacol. 2021 Apr;178(7):1684-1704. doi: 10.1111/bph.15392. Epub 2021 Feb 23. PMID: 33496352.