AR-A014418 | SN 4521 | CAS#487021-52-3 | GSK-3β Inhibitor

MedKoo Cat#: 524255 | Name: AR-A014418

Description:

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

AR-A014418 , also known as SN 4521, is a labeled Glycogen Synthase Kinase 3β (GSK-3β) inhibitor. AR-A014418 suppresses pancreatic cancer cell growth via inhibition of GSK-3-mediated Notch1 expression. AR-A014418 decreases neuropathic pain in mice: evidence for the mechanisms of action. AR-A014418 and B6B3O prevent human immunodeficiency virus-mediated neurotoxicity in primary human neurons.

Chemical Structure

AR-A014418

CAS#487021-52-3

Theoretical Analysis

MedKoo Cat#: 524255

Name: AR-A014418

CAS#: 487021-52-3

Chemical Formula: C12H12N4O4S

Exact Mass: 308.0579

Molecular Weight: 308.31

Elemental Analysis: C, 46.75; H, 3.92; N, 18.17; O, 20.76; S, 10.40

Price and Availability

Size	Price	Availability
100mg	USD 550.00	2 Weeks
200mg	USD 950.00	2 Weeks
500mg	USD 1,650.00	2 Weeks
1g	USD 2,750.00	2 Weeks
2g	USD 3,850.00	2 Weeks
5g	USD 5,750.00	2 Weeks

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Synonym

SN 4521; SN4521; SN-4521; AR-A 014418; AR-A014418; AR-A-014418; AR-AO-14418; GSK-3beta Inhibitor VIII; AR 0133418; AR0133418; AR-0133418

IUPAC/Chemical Name

N-(4-Methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea

InChi Key

YAEMHJKFIIIULI-UHFFFAOYSA-N

InChi Code

InChI=1S/C12H12N4O4S/c1-20-9-4-2-8(3-5-9)6-13-11(17)15-12-14-7-10(21-12)16(18)19/h2-5,7H,6H2,1H3,(H2,13,14,15,17)

SMILES Code

O=C(NC1=NC=C([N+]([O-])=O)S1)NCC2=CC=C(OC)C=C2

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, not in water

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:

AR-A014418 is a potent, selective and ATP-competitive GSK3β inhibitor (IC50=104 nM; Ki=38 nM).

In vitro activity:

AR-A014418 treatment decreased the survival of U937 cells with a half-maximal inhibitory concentration (IC50) of approximately 5 µM after a 24 hr treatment (Figure 1a). The AR-A014418 treatment caused a marked reduction in proliferation (Figure 1b) and the colony-forming ability (Figure 1c) of U937 cells. These results indicate that AR-014418 elicits apoptosis in U937 cells. Transfection of constitutively active GSK3β (59A; CA-GSK3β) increased the survival of AR-A014418-treated U937 cells (Figure 1g), indicating the causal role of GSK3β suppression in AR-A014418-induced cell death. Reference: J Cell Physiol. 2021 Jan;236(1):570-586. https://pubmed.ncbi.nlm.nih.gov/32572959/

In vivo activity:

However, the pre-emptive treatment of AR-A014418 decreased the apoptotic cells in ipsilateral laminae I, II, III [F(2, 24)=100.9; P<0.0001]; IV, V [F(2, 24)=39.59; P<0.0001], and X [F(2, 24)=15.98; P<0.0001] in the SNL group. The one-way ANOVA results also revealed a significant increase in the TUNEL-positive cells in contralateral laminae I, II, III, IV, V, and X in the SNL group, in comparison to the sham-operated rats. However, the pre-emptive treatment of AR-A014418 decreased the apoptotic cells in the contralateral laminae I, II, III [F(2, 24)=51.24; P<0.0001]; IV, V [F(2, 24)=22; P<0.0001], and X [F(2, 24)=8.22; P<0.001] in the SNL group. Reference: Basic Clin Neurosci. 2020 Jan-Feb; 11(1): 15–30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253818/

	Solvent	mg/mL	mM
Solubility
	DMSO	55.5	179.88

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 308.31 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.

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. Lee YC, Shi YJ, Wang LJ, Chiou JT, Huang CH, Chang LS. GSK3β suppression inhibits MCL1 protein synthesis in human acute myeloid leukemia cells. J Cell Physiol. 2021 Jan;236(1):570-586. doi: 10.1002/jcp.29884. Epub 2020 Jun 22. PMID: 32572959. 2. Kawahara N, Mizutani A, Matsubara S, Takeda Y, Kobayashi H. GSK-3β mediates the effects of HNF-1β overexpression in ovarian clear cell carcinoma. Exp Ther Med. 2020 Nov;20(5):122. doi: 10.3892/etm.2020.9250. Epub 2020 Sep 21. PMID: 33005248; PMCID: PMC7523276. 3. Rashvand M, Danyali S, Manaheji H. The Potential Role of Glycogen Synthase Kinase-3β in Neuropathy-Induced Apoptosis in Spinal Cord. Basic Clin Neurosci. 2020 Jan-Feb;11(1):15-30. doi: 10.32598/bcn.11.1.1. Epub 2020 Jan 1. PMID: 32483472; PMCID: PMC7253818. 4. Yan X, Li Z, Li H, Liu P, Zhao Z, Cheng S, Wang Z, Zhang Q. Inhibition Of Glycogen Synthase Kinase 3 Beta Suppresses The Growth And Survival Of Skull Base Chordoma Cells By Downregulating Brachyury Expression. Onco Targets Ther. 2019 Nov 18;12:9783-9791. doi: 10.2147/OTT.S218930. PMID: 31819479; PMCID: PMC6874116.

In vitro protocol:

In vivo protocol:

1. Rashvand M, Danyali S, Manaheji H. The Potential Role of Glycogen Synthase Kinase-3β in Neuropathy-Induced Apoptosis in Spinal Cord. Basic Clin Neurosci. 2020 Jan-Feb;11(1):15-30. doi: 10.32598/bcn.11.1.1. Epub 2020 Jan 1. PMID: 32483472; PMCID: PMC7253818. 2. Yan X, Li Z, Li H, Liu P, Zhao Z, Cheng S, Wang Z, Zhang Q. Inhibition Of Glycogen Synthase Kinase 3 Beta Suppresses The Growth And Survival Of Skull Base Chordoma Cells By Downregulating Brachyury Expression. Onco Targets Ther. 2019 Nov 18;12:9783-9791. doi: 10.2147/OTT.S218930. PMID: 31819479; PMCID: PMC6874116.

1: Kunnimalaiyaan S, Gamblin TC, Kunnimalaiyaan M. Glycogen synthase kinase-3 inhibitor AR-A014418 suppresses pancreatic cancer cell growth via inhibition of GSK-3-mediated Notch1 expression. HPB (Oxford). 2015 Sep;17(9):770-6. doi: 10.1111/hpb.12442. Epub 2015 Jul 6. PubMed PMID: 26147011; PubMed Central PMCID: PMC4557650. 2: Tunçdemir M, Yıldırım A, Karaoğlan A, Akdemir O, Oztürk M. AR-A014418 as a glycogen synthase kinase-3 inhibitor: anti-apoptotic and therapeutic potential in experimental spinal cord injury. Neurocirugia (Astur). 2013 Jan-Feb;24(1):22-32. doi: 10.1016/j.neucir.2011.12.006. Epub 2012 Oct 30. PubMed PMID: 23116585. 3: Mazzardo-Martins L, Martins DF, Stramosk J, Cidral-Filho FJ, Santos AR. Glycogen synthase kinase 3-specific inhibitor AR-A014418 decreases neuropathic pain in mice: evidence for the mechanisms of action. Neuroscience. 2012 Dec 13;226:411-20. doi: 10.1016/j.neuroscience.2012.09.020. Epub 2012 Sep 19. PubMed PMID: 23000630. 4: Hicks JW, Wilson AA, Rubie EA, Woodgett JR, Houle S, Vasdev N. Towards the preparation of radiolabeled 1-aryl-3-benzyl ureas: Radiosynthesis of [(11)C-carbonyl] AR-A014418 by [(11)C]CO(2) fixation. Bioorg Med Chem Lett. 2012 Mar 1;22(5):2099-101. doi: 10.1016/j.bmcl.2011.12.139. Epub 2012 Jan 10. PubMed PMID: 22321216. 5: Martins DF, Rosa AO, Gadotti VM, Mazzardo-Martins L, Nascimento FP, Egea J, López MG, Santos AR. The antinociceptive effects of AR-A014418, a selective inhibitor of glycogen synthase kinase-3 beta, in mice. J Pain. 2011 Mar;12(3):315-22. doi: 10.1016/j.jpain.2010.06.007. Epub 2010 Aug 12. PubMed PMID: 20705523. 6: Nguyen TB, Lucero GR, Chana G, Hult BJ, Tatro ET, Masliah E, Grant I, Achim CL, Everall IP; HIV Neurobehavioral Research Group. Glycogen synthase kinase-3beta (GSK-3beta) inhibitors AR-A014418 and B6B3O prevent human immunodeficiency virus-mediated neurotoxicity in primary human neurons. J Neurovirol. 2009 Sep;15(5-6):434-8. doi: 10.1080/13550280903168131. PubMed PMID: 19688630; PubMed Central PMCID: PMC3065998. 7: Vasdev N, Garcia A, Stableford WT, Young AB, Meyer JH, Houle S, Wilson AA. Synthesis and ex vivo evaluation of carbon-11 labelled N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea ([11C]AR-A014418): a radiolabelled glycogen synthase kinase-3beta specific inhibitor for PET studies. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5270-3. Epub 2005 Oct 3. PubMed PMID: 16202587. 8: Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004 Dec;7(4):387-90. Epub 2004 Jul 26. PubMed PMID: 15315719. 9: Bhat R, Xue Y, Berg S, Hellberg S, Ormö M, Nilsson Y, Radesäter AC, Jerning E, Markgren PO, Borgegård T, Nylöf M, Giménez-Cassina A, Hernández F, Lucas JJ, Díaz-Nido J, Avila J. Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 2003 Nov 14;278(46):45937-45. Epub 2003 Aug 19. PubMed PMID: 12928438.