Folate analogs including aminopterin, methotrexate, pemetrexed, and pralatexate are used for the treatment of cancers to inhibit cytosolic one-carbon metabolism enzymes including dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), with an indirect effect on de novo purine biosynthetic metabolism [27]. Here, TYMS is linked to cancer.