Pemetrexed

Pemetrexed is a multi-targeted antifolate with antitumor activity. It potently inhibits folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase (Ki = 109 nM), dihydrofolate reductase (Ki = 7 nM), glycinamide ribonucleotide formyltransferase (Ki = 9.3 μM), and aminoimidazole carboxamide ribonucleotide formyltransferase (Ki = 3.6 μM) .1 A clinically useful anticancer agent.2 Indirectly activates the metabolic kinase AMPK and consequently influences the mTORC1 pathway in human carcinomas.3 Activation of AMPK is associated with pemetrexed resistance.4 Induces G0/G1-phase cell cycle arrest in esophageal squamous cell carcinoma cells.5