GSK-2126458

• CAT Number: I000371
• CAS Number: 1086062-66-9
• Molecular Formula: C₂₅H₁₇F₂N₅O₃S
• Molecular Weight: 505.5
• Purity: ≥95%
• Target: mTOR
• Solubility: DMSO ≥98mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL
• Storage: 3 years -20℃ powder
• IC50: 0.019 nM/0.13 nM/0.024 nM/0.06 nM and 0.18 nM/0.3 nM (p110α/β/δ/γ, mTORC1/2) [1]
• IUPAC Name: 2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)pyridin-3-yl]benzenesulfonamide
• InChI: InChI=1S/C25H17F2N5O3S/c1-35-25-23(32-36(33,34)24-5-3-18(26)12-21(24)27)11-17(13-29-25)15-2-4-22-20(10-15)19(7-8-28-22)16-6-9-30-31-14-16/h2-14,32H,1H3
• InChIKey: CGBJSGAELGCMKE-UHFFFAOYSA-N
• SMILES: COC1=C(C=C(C=N1)C2=CC3=C(C=CN=C3C=C2)C4=CN=NC=C4)NS(=O)(=O)C5=C(C=C(C=C5)F)F

GSK-2126458 (Cat.No:I000371) is a small molecule inhibitor developed by GlaxoSmithKline (GSK). It targets the mitogen-activated protein kinase (MAPK)-activated protein kinase 5 (MK5), an enzyme involved in cellular signaling pathways. GSK-2126458 has shown potential in preclinical studies for its anti-inflammatory and anti-cancer properties, making it a candidate for therapeutic development in various diseases.

Reference

1:The dual PI3K/mTOR inhibitor GSK2126458 is effective for treating solid renal tumours in Tsc2+/- mice through suppression of cell proliferation and induction of apoptosis. Narov K, Yang J, Samsel P, Jones A, Sampson JR, Shen MH.Oncotarget. 2017 Apr 19. doi: 10.18632/oncotarget.17215. [Epub ahead of print] PMID: 28472760 Free Article2:A phase Ib dose-escalation study of the MEK inhibitor trametinib in combination with the PI3K/mTOR inhibitor GSK2126458 in patients with advanced solid tumors. Grilley-Olson JE, Bedard PL, Fasolo A, Cornfeld M, Cartee L, Razak AR, Stayner LA, Wu Y, Greenwood R, Singh R, Lee CB, Bendell J, Burris HA, Del Conte G, Sessa C, Infante JR.Invest New Drugs. 2016 Dec;34(6):740-749. Epub 2016 Jul 23. PMID: 27450049 3:Factors Influencing the Central Nervous System Distribution of a Novel Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Inhibitor GSK2126458: Implications for Overcoming Resistance with Combination Therapy for Melanoma Brain Metastases. Vaidhyanathan S, Wilken-Resman B, Ma DJ, Parrish KE, Mittapalli RK, Carlson BL, Sarkaria JN, Elmquist WF.J Pharmacol Exp Ther. 2016 Feb;356(2):251-9. doi: 10.1124/jpet.115.229393. Epub 2015 Nov 24. PMID: 26604245 Free PMC Article4:First-in-Human Phase I Study of GSK2126458, an Oral Pan-Class I Phosphatidylinositol-3-Kinase Inhibitor, in Patients with Advanced Solid Tumor Malignancies. Munster P, Aggarwal R, Hong D, Schellens JH, van der Noll R, Specht J, Witteveen PO, Werner TL, Dees EC, Bergsland E, Agarwal N, Kleha JF, Durante M, Adams L, Smith DA, Lampkin TA, Morris SR, Kurzrock R.Clin Cancer Res. 2016 Apr 15;22(8):1932-9. doi: 10.1158/1078-0432.CCR-15-1665. Epub 2015 Nov 24. PMID: 26603258 Free Article5:Liquid chromatography-tandem mass spectrometric assay for the PI3K/mTOR inhibitor GSK2126458 in mouse plasma and tumor homogenate. Dolman ME, Westerhout EM, Hamdi M, Schellens JH, Beijnen JH, Sparidans RW.J Pharm Biomed Anal. 2015 Mar 25;107:403-8. doi: 10.1016/j.jpba.2015.01.026. Epub 2015 Jan 19. PMID: 25659532 6:Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma. Liu T, Sun Q, Li Q, Yang H, Zhang Y, Wang R, Lin X, Xiao D, Yuan Y, Chen L, Wang W.Mol Cancer Ther. 2015 Feb;14(2):429-39. doi: 10.1158/1535-7163.MCT-14-0548. Epub 2014 Dec 12. PMID: 25504751 Free Article7:In vitro assessment of antitumor activities of the PI3K/mTOR inhibitor GSK2126458. Albawardi A, Al Ayyan M, Al Bashir M, Souid AK, Almarzooqi S.Cancer Cell Int. 2014 Sep 24;14(1):90. doi: 10.1186/s12935-014-0090-z. eCollection 2014. PMID: 25298748 Free PMC Article8:[11C]GSK2126458 and [18F]GSK2126458, the first radiosynthesis of new potential PET agents for imaging of PI3K and mTOR in cancers. Wang M, Gao M, Miller KD, Sledge GW, Zheng QH.Bioorg Med Chem Lett. 2012 Feb 15;22(4):1569-74. doi: 10.1016/j.bmcl.2011.12.136. Epub 2012 Jan 10. PMID: 22297110 9:Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells. Leung E, Kim JE, Rewcastle GW, Finlay GJ, Baguley BC.Cancer Biol Ther. 2011 Jun 1;11(11):938-46. Epub 2011 Jun 1. PMID: 21464613 Free PMC Article10:Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin. Knight SD, Adams ND, Burgess JL, Chaudhari AM, Darcy MG, Donatelli CA, Luengo JI, Newlander KA, Parrish CA, Ridgers LH, Sarpong MA, Schmidt SJ, Van Aller GS, Carson JD, Diamond MA, Elkins PA, Gardiner CM, Garver E, Gilbert SA, Gontarek RR, Jackson JR, Kershner KL, Luo L, Raha K, Sherk CS, Sung CM, Sutton D, Tummino PJ, Wegrzyn RJ, Auger KR, Dhanak D.ACS Med Chem Lett. 2010 Jan 19;1(1):39-43. doi: 10.1021/ml900028r. eCollection 2010 Apr 8. PMID: 24900173 Free PMC Article