TYMS and neoplasm: By replacing the N-5, N-8 and N-10 atoms and modifying the side chains of the methotrexate molecule, it was possible to synthesize drugs that retain their inherent ability to form stable polyglutamates inside the cell, but better penetrate the tumor [15], such as the following: raltitrexed, a thymidylate synthase inhibitor; lometrexol, a purine synthesis inhibitor; and pemetrexed, which combines both mechanisms of action [16].