GSK-3 Inhibitor, AR-A014418

• CAT Number: I003717
• CAS Number: 487021-52-3
• Molecular Formula: C₁₂H₁₂N₄O₄S
• Molecular Weight: 308.31
• Purity: ≥95%
• Synonyms: 1-[(4-methoxyphenyl)methyl]-3-(5-nitro-1,3-thiazol-2-yl)urea
• Target: GSK-3
• Solubility: 10 mM in DMSO
• Storage: 2-8°C
• IC50: 104 +/- 27 nM
• InChI: 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)
• InChIKey: YAEMHJKFIIIULI-UHFFFAOYSA-N
• SMILES: COC1=CC=C(C=C1)CNC(=O)NC2=NC=C(S2)[N+](=O)[O-]

AR-A014418（Cat No.:I003717）, also known as GSK-3β Inhibitor VIII, is a selective and ATP-competitive inhibitor of glycogen synthase kinase-3β (GSK3β). It exhibits an IC50 value of 104 nM and a Ki value of 38 nM in cell-free assays. Notably, AR-A014418 demonstrates high selectivity for GSK3β, with no significant inhibitory effects on the other 26 kinases tested. By targeting GSK3β, this inhibitor offers a valuable tool for studying the role of GSK3β in various biological processes and may hold therapeutic potential in conditions where GSK3β dysregulation is implicated.

Reference

1:Glycogen synthase kinase-3 inhibitor AR-A014418 suppresses pancreatic cancer cell growth via inhibition of GSK-3-mediated Notch1 expression. Kunnimalaiyaan S, Gamblin TC, Kunnimalaiyaan M.HPB (Oxford). 2015 Sep;17(9):770-6. doi: 10.1111/hpb.12442. Epub 2015 Jul 6. PMID: 26147011 Free PMC Article2:AR-A014418 as a glycogen synthase kinase-3 inhibitor: anti-apoptotic and therapeutic potential in experimental spinal cord injury. Tunçdemir M, Yıldırım A, Karaoğlan A, Akdemir O, Oztürk M.Neurocirugia (Astur). 2013 Jan-Feb;24(1):22-32. doi: 10.1016/j.neucir.2011.12.006. Epub 2012 Oct 30. PMID: 23116585 3:Glycogen synthase kinase 3-specific inhibitor AR-A014418 decreases neuropathic pain in mice: evidence for the mechanisms of action. Mazzardo-Martins L, Martins DF, Stramosk J, Cidral-Filho FJ, Santos AR.Neuroscience. 2012 Dec 13;226:411-20. doi: 10.1016/j.neuroscience.2012.09.020. Epub 2012 Sep 19. PMID: 23000630 4:Towards the preparation of radiolabeled 1-aryl-3-benzyl ureas: Radiosynthesis of [(11)C-carbonyl] AR-A014418 by [(11)C]CO(2) fixation. Hicks JW, Wilson AA, Rubie EA, Woodgett JR, Houle S, Vasdev N.Bioorg Med Chem Lett. 2012 Mar 1;22(5):2099-101. doi: 10.1016/j.bmcl.2011.12.139. Epub 2012 Jan 10. PMID: 22321216 5:The antinociceptive effects of AR-A014418, a selective inhibitor of glycogen synthase kinase-3 beta, in mice. Martins DF, Rosa AO, Gadotti VM, Mazzardo-Martins L, Nascimento FP, Egea J, López MG, Santos AR.J Pain. 2011 Mar;12(3):315-22. doi: 10.1016/j.jpain.2010.06.007. Epub 2010 Aug 12. PMID: 20705523 6:Glycogen synthase kinase-3beta (GSK-3beta) inhibitors AR-A014418 and B6B3O prevent human immunodeficiency virus-mediated neurotoxicity in primary human neurons. Nguyen TB, Lucero GR, Chana G, Hult BJ, Tatro ET, Masliah E, Grant I, Achim CL, Everall IP; HIV Neurobehavioral Research Group..J Neurovirol. 2009 Sep;15(5-6):434-8. doi: 10.1080/13550280903168131. PMID: 19688630 Free PMC Article7: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. Vasdev N, Garcia A, Stableford WT, Young AB, Meyer JH, Houle S, Wilson AA.Bioorg Med Chem Lett. 2005 Dec 1;15(23):5270-3. Epub 2005 Oct 3. PMID: 16202587 8:AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Gould TD, Einat H, Bhat R, Manji HK.Int J Neuropsychopharmacol. 2004 Dec;7(4):387-90. Epub 2004 Jul 26. PMID: 15315719 9:Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. 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.J Biol Chem. 2003 Nov 14;278(46):45937-45. Epub 2003 Aug 19. PMID: 12928438 Free Article