Pemetrexed (LY231514) disodium is a classical antifolate with novel mechanisms, exerting antitumor effects through simultaneous and multipie inhibition of several key folate-requiring enzymes via its polyglutamated metabolites. Pemetrexed (LY231514) demonstrates substantial potency toward the enzyme FPGS (Km=1.6 μM and Vmax/Km=621). Polyglutamation and its metabolites likely play crucial roles in determining the selectivity and antitumor activity of Pemetrexed. While LY231514 moderately inhibits TS (Ki=340 nM, recombinant mouse), its pentaglutamate form is 100-fold more potent (Ki=3.4 nM), making Pemetrexed one of the most potent folate-based TS inhibitors [1].
体内研究
The survival of mice treated with PC61 plus Pemetrexed significantly exceeds that of other groups. In survival analysis, markedly improved survival is observed in mice treated with PC61 plus Pemetrexed compared to those receiving PC61 alone, rat IgG plus Pemetrexed, or no treatment [2].
体外研究
Pemetrexed (LY231514) disodium is a classical antifolate with novel mechanisms, exerting antitumor effects through simultaneous and multipie inhibition of several key folate-requiring enzymes via its polyglutamated metabolites. Pemetrexed (LY231514) demonstrates substantial potency toward the enzyme FPGS (Km=1.6 μM and Vmax/Km=621). Polyglutamation and its metabolites likely play crucial roles in determining the selectivity and antitumor activity of Pemetrexed. While LY231514 moderately inhibits TS (Ki=340 nM, recombinant mouse), its pentaglutamate form is 100-fold more potent (Ki=3.4 nM), making Pemetrexed one of the most potent folate-based TS inhibitors [1].
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