Pemetrexed-disodium-hemipenta-hydrate-LY231514-disodium-hemipenta-hydrate-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEPemetrexed disodium hemipenta hydrateCat. No.: HY-13781CAS No.: 357166-30-4Synonyms: LY231514 (disodium hemipenta hydrate)分式: CHNO . / HO . Na分量: 516.41作靶点: Antifolate; Autophagy作通路: Cell Cycle/DNA Damage; Autophagy储存式: Powder -

2、20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 H2O : 29 mg/mL (56.16 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.9364 mL 9.6822 mL 19.3645 mL5 mM 0.3873 mL 1.9364 mL 3.8729 mL10 mM 0.1936 mL 0.9682 mL 1.9364 mL请根据产品在不同溶剂中的溶解度，选择

3、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 Pemetrexed disodium hemipenta hydrate种叶酸拮抗剂 (antifolate)。抑制胸苷酸合成酶 (TS)，氢叶酸还原酶 (DHFR) 和氨酰胺核苷酸甲酰转移酶 (GARFT)，Ki 分别为 1.3 nM，7.2 nM 和 65 nM。IC50 & Target Ki: 1.3 nM (TS), 7.2 nM (DHFR), 65 nM (GARFT) 11/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 P

4、emetrexed (LY231514) disodium is a novel classical antifolate, the antitumor activity of which may resultfrom simultaneous and multipie inhibition of several key folate-requiring enzymes via its polyglutamatedmetabolites. Pemetrexed (LY231514) is one of the best substrates that is known for the enzy

5、me FPGS(Km=1.6 M and Vmax/Km=621). It is likely that polyglutamation and the polyglutamated metabolites ofLY231514 play profound roles in determining both the selectivity and the antitumor activity of this novelagent. Whereas LY23l5l4 only moderately inhibits TS (Ki=340 nM, recombinant mouse), the p

6、entaglutamateof LY23l5l4 is 100-fold more potent (Ki=3.4 nM), making LY231514 one of the most potent folate-based TSinhibitors 1.体内研究 The group of mice treated with PC61 plus Pemetrexed demonstrates statistically longer survival than othergroups. In a survival analysis, significantly better survival

7、 is observed in the group of mice treated with PC61plus Pemetrexed compare with those treated with PC61 alone, rat IgG plus Pemetrexed, or no treatment 2.PROTOCOLKinase Assay 1 AICARFT inhibition assays are carried out at room temperature by monitoring the formation of 6S-5,6,7,8-tetrahydrofolate fr

8、om 10-formyl-6R,S-5,6,7,8-tetrahydrofolate at A298. All solutions are purged with N2 gasprior to use. The reaction solution contains 33 mM Tris-Cl, pH 7.4, 25 mM KCl, 5 mM 2-Mercaptoethanol,0.05 mM AICA ribonucleotide, and 16 nM (2 milliunits/mL) of AICARFT. 10-Formyl-6R,S-5,6,7,8-tetrahydrofolate c

9、oncentrations of 0.037, 0.074, and 0.145 mM are used (0.61, 1.23, and 2.45 times its Kmvalue, respectively). LY231514 is tested as an inhibitor at 0.08-0.8 mM (four concentrations). When the tri-and pentaglutamates of LY231514 are used as inhibitors, the concentrations are 0.0005-0.009 mM (eightconc

10、entrations). Enzyme assays are initiated by the addition of enzyme. Data is analyzed using theENZFITTER program for competitive inhibition.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 Dose-response curves are generated to determine the c

11、oncentration required for 50% inhibition of growth(IC50). Pemetrexed is dissolved initially in DMSO at a concentration of 4 mg/mL and further diluted with cellculture medium to the desired concentration. CCRF-CEM leukemia cells in complete medium are added to24-well Cluster plates at a final concent

12、ration of 4.8104 cells/well in a total volume of 2 mL. Test compoundsat various concentrations are added to duplicate wells so that the final volume of DMSO is 0.5%. The platesare incubated for 72 h at 37C in an atmosphere of 5% CO2 in air. At the end of the incubation, cell numbersare determined on

13、 a ZBI Coulter counter. Control wells usually contain 4105 to 6105 cells at the end of theincubation. For several studies, IC50s are determined for each compound in the presence of either 300 MAICA, 5 M thymidine, 100 M hypoxanthine, or combination of 5 M hymidine plus 100 M hypoxanthine1.MCE has no

14、t independently confirmed the accuracy of these methods. They are for reference only.Animal Dose-response curves are generated to determine the concentration required for 50% inhibition of growthAdministration 1 (IC50). Pemetrexed is dissolved initially in DMSO at a concentration of 4 mg/mL and furt

15、her diluted with cellculture medium to the desired concentration. CCRF-CEM leukemia cells in complete medium are added to24-well Cluster plates at a final concentration of 4.8l04 cells/well in a total volume of 2 mL. Test compoundsat various concentrations are added to duplicate wells so that the fi

16、nal volume of DMSO is 0.5%. The plates2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEare incubated for 72 h at 37C in an atmosphere of 5% CO2 in air. At the end of the incubation, cell numbersare determined on a ZBI Coulter counter. Control wells usually contain 4105 to 6105 cells at the end of th

17、eincubation. For several studies, IC50s are determined for each compound in the presence of either 300 MAICA, 5 M thymidine, 100 M hypoxanthine, or combination of 5 M hymidine plus 100 M hypoxanthine1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产

18、品发表的科研献 J Mol Med (Berl). 2019 Jun 14. Beilstein J Org Chem. 2017 Oct 25;13:2252-2263. Faculty of the Graduate School of Biomedical Sciences. The University of Texas Southwestern Medical Center. Oct 1. 2015.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Shih C, et al. LY231514, a pyrrolo2,3-dpyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Res. 1997Mar 15;57(6):1116-23.2. Anraku M, et al. Synergistic antitumor effects of regulatory T cell blockade combined wi