In the Table, methotrexate, an inhibitor of dihydrofolate reductase (DHFR),when used as seed, was matched most closely with trimetrexate, a potent lipophilic antifolate (32). DHFR is required for the conversion of the pyrimidine nucleotide uridine monophosphate to thymidine monophosphate, and inhibitors of the enzyme thus indirectly interfere with nucleic acid biosynthesis. This relationship probably explains why several pyrimidine biosynthesis inhibitors (brequinar, pyrazofurin, DON, cyclopentenylcytosine, AT-125, dichloroallyl lawsone, and 3-deazauridine) were good COMPARE matches when methotrexate was the seed compound. These agents were followed by another antifolate, Soluble Bakers Antifol (NSC 139105).

More information on compounds mentioned
Compound NSC Number 2D Structure 3D Structure Cell Inhibition Data
methotrexate 740 2D 3D Cell Data
soluble Baker's Antifol 139105 2D 3D Cell Data
brequinar sodium 368390 2D 3D Cell Data
dichloroallyl lawsone 126771 2D 3D Cell Data
pyrazofurin 143095 2D 3D Cell Data
DON 7365 2D 3D Cell Data
AT-125 (acivicin) 163501 2D 3D Cell Data
3-deazauridine 126849 2D 3D Cell Data
cyclopentenylcytosine 375575 2D 3D Cell Data