Pemetrexed
Pemetrexed
Pemetrexed is an antifolate preparation with a core pyrrolopyrimidine group in its structure. It inhibits cell replication and thus tumor growth by destroying the normal metabolic process of intracellular folate dependence. In vitro studies have shown that pemetrexed can inhibit the activity of thymidylate synthase, dihydrofolate reductase and glycinamide nucleotide formyltransferase, which are enzymes necessary for the synthesis of folate and participate in the bioresynthesis of thymine nucleotides and purine nucleotides. Pemetrexed enters the cell through the carrier carrying folic acid and the folate binding protein transport system on the cell membrane. Once pemetrexed enters the cell, it is converted into polyglutamate under the action of folylpolyglutamate synthetase. Polyglutamate remains in the cell and becomes an inhibitor of thymidylate synthase and glycinamide nucleotide formyltransferase. Polyglutamate is a time-concentration dependent process in tumor cells, while the concentration in normal tissues is very low. The half-life of polyglutamate metabolites in tumor cells is prolonged, thereby prolonging the duration of drug action in tumor cells. Preclinical studies have shown that pemetrexed can inhibit the growth of mesothelioma cell lines (MSTO-211H, NCI-H2052) in vitro. Studies on the mesothelioma cell line MSTO-211H have shown that pemetrexed combined with cisplatin has a synergistic effect.