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).
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 |