Thymidylate Synthase (TS) (EC 2.1.1.45) converts deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), which is essential for DNA biosynthesis. TS is a critical target for the fluoropyrimidines, an important group of antineoplastic drugs that are widely used in the treatment of solid tumors. Both 5-FU and fluorodeoxyuridine are converted in tumor cells to FdUMP which inactivates TS by formation of a ternary covalent complex in the presence of the folate cofactor 5,10-methylenetetrahydrofolate. Expression of TS protein is associated with response to 5-fluorouracil (5-FU) in human colorectal, gastric, head and neck, and breast carcinomas.