LY2090314 _GSK-3 抑制剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELY2090314Cat. No.: HY-16294CAS No.: 603288-22-8分式: CHFNO分量: 512.53作靶点: GSK-3作通路: PI3K/Akt/mTOR; Stem Cell/Wnt储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 31 mg/mL (60.48 mM)* means solub

2、le, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.9511 mL 9.7555 mL 19.5111 mL5 mM 0.3902 mL 1.9511 mL 3.9022 mL10 mM 0.1951 mL 0.9756 mL 1.9511 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 LY2090314种有效的 GSK-3 抑制剂，抑制 GSK-3 和 GSK-3，IC50 值分别为 1.5 n

3、M 和 0.9 nM。IC50 & Target GSK-3 GSK-30.9 nM (IC50) 1.5 nM (IC50)体外研究LY2090314 (20 nM) promotes a time-dependent stabilization of -catenin total protein as well as an induction1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEof Axin2. LY2090314 is highly selective towards GSK3 as demonstrated by its f

4、old selectivity relative to alarge panel of kinases. LY2090314 potently induces apoptotic cell death in a panel of melanoma cell linesirrespective of BRAF mutation status. Cell death induced by LY2090314 is dependent on -catenin andGSK3 knockdown increases the sensitivity of cells to LY2090314. LY20

5、90314 remains active in cell linesresistant to Vemurafenib and has an independent mechanism of action 2.体内研究 LY2090314 exhibits high clearance (approximating hepatic blood flow) and a moderate volume of distribution(appr 1-2 L/kg) resulting in rapid elimination (half-life appr 0.4, 0.7, and 1.8-3.4

6、hours in rats, dogs, andhumans, respectively). LY2090314 is rapidly cleared by extensive metabolism with negligible circulatingmetabolite exposures due to biliary excretion of metabolites into feces with no apparent intestinalreabsorption 1. LY2090314 (25 mg/kg Q3D, i.v.) elevates Axin2 gene express

7、ion in vivo, demonstratessingle agent activity in the A375 xenograft model of melanoma and enhances the efficacy of DTIC 2.PROTOCOLAnimal Five million A375 human melanoma cancer cells are injected S.C. in the flank of female 6 to 8 week oldAdministration 2 athymic nude mice in a 1:1 mixture with mat

8、rigel. Mice are monitored daily for palpable tumors. When tumorsreach appr 100 mm2 mice are randomized into groups receiving either LY2090314 (25 mg/kg Q3D) orvehicle (20% Captisol/0.01N HCl) via i.v. administration. Tumor volume (measured by calipers) and animalbody weight are recorded twice weekly

9、. Tumor volumes are calculated using the formula: (a2 b)/2 (a beingthe smaller and b being the larger dimension of the tumor). For combination studies with DTIC (60 mg/kgQD), LY2090314 is dosed at 2.5 mg/kg Q3D and tumor growth monitored.MCE has not independently confirmed the accuracy of these meth

10、ods. They are for reference only.户使本产品发表的科研献 Stem Cell Reports. 2018 Dec 11;11(6):1539-1550. J Biol Chem. 2016 Dec 23;291(52):26875-26885. Int Immunopharmacol. 2019 Jun. Harvard Medical School LINCS LIBRARYSee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Zamek-Gliszczynski MJ, e

11、t al. Pharmacokinetics, metabolism, and excretion of the glycogen synthase kinase-3 inhibitor LY2090314 inrats, dogs, and humans: a case study in rapid clearance by extensive metabolism with low circulating metabolite exposure. Dr2. Atkinson JM, et al. Activating the Wnt/-Catenin Pathway for the Treatment of Melanoma-Application of LY2090314, a Novel SelectiveInhibitor of Glycogen Synthase Kinase-3. PLoS One. 2015 Apr 27;10(4):e0125028.McePdfHeightCaution: Product h