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Pemetrexed disodium

MCE China：Pemetrexed disodium

Brand：MedChemExpress (MCE)

Cat. No.HY-10820A

CAS：150399-23-8

Synonyms：LY231514 disodium

Purity：99.79%

Storage：4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Shipping：Room temperature in continental US; may vary elsewhere.

Description：Pemetrexed disodium (LY231514 disodium) is an antifolate, the Kis of the pentaglutamate of Pemetrexed disodium are 1.3, 7.2, and 65 nM for inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), respectively.

In Vitro：Pemetrexed (LY231514) disodium is a novel classical antifolate, the antitumor activity of which may result from simultaneous and multipie inhibition of several key folate-requiring enzymes via its polyglutamated metabolites. Pemetrexed (LY231514) is one of the best substrates that is known for the enzyme FPGS (Km=1.6 μM and Vmax/Km=621). It is likely that polyglutamation and the polyglutamated metabolites of LY231514 play profound roles in determining both the selectivity and the antitumor activity of this novel agent. Whereas LY23l5l4 only moderately inhibits TS (Ki=340 nM, recombinant mouse), the pentaglutamate of LY23l5l4 is 100-fold more potent (Ki=3.4 nM), making LY231514 one of the most potent folate-based TS inhibitors[1].

In Vivo：The group of mice treated with PC61 plus Pemetrexed demonstrates statistically longer survival than other groups. In a survival analysis, significantly better survival is observed in the group of mice treated with PC61 plus Pemetrexed compare with those treated with PC61 alone, rat IgG plus Pemetrexed, or no treatment[2].

Animal Administration：Mice[2] Female CBA mice and female NOD/SCID mice (NOD.CB17-Prkdcscid) at 6-8 wk of age are used. Premetrexed (100 mg/kg) is given i.p. from days 4-8 (5 consecutive d) to tumor-bearing mice to explore the synergistic effect when combined with anti-CD25 Ab or IgG control. The dose and schedule used for Pemetrexed in the current study is determined based on previous studies in mice.

Cell Assay：Dose-response curves are generated to determine the concentration required for 50% inhibition of growth (IC50). Pemetrexed is dissolved initially in DMSO at a concentration of 4 mg/mL and further diluted with cell culture medium to the desired concentration. CCRF-CEM leukemia cells in complete medium are added to 24-well Cluster plates at a final concentration of 4.8×104 cells/well in a total volume of 2 mL. Test compounds at various concentrations are added to duplicate wells so that the final volume of DMSO is 0.5%. The plates are incubated for 72 h at 37°C in an atmosphere of 5% CO2 in air. At the end of the incubation, cell numbers are determined on a ZBI Coulter counter. Control wells usually contain 4×105 to 6×105 cells at the end of the incubation. For several studies, IC50s are determined for each compound in the presence of either 300 μM AICA, 5 μM thymidine, 100 μM hypoxanthine, or combination of 5 μM hymidine plus 100 μM hypoxanthine[1].

IC50 & Target：Ki: 1.3 nM (TS), 7.2 nM (DHFR), 65 nM (GARFT)[1] Cellular Effect Cell Line Type Value Description References

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References：

[1]. Shih C, et al. LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. Cancer Res. 1997 Mar 15;57(6):1116-23.  [Content Brief]

[2]. Anraku M, et al. Synergistic antitumor effects of regulatory T cell blockade combined with pemetrexed in murine malignantmesothelioma. J Immunol. 2010 Jul 15;185(2):956-66.  [Content Brief]