Inhibitors of DHFR, such as methotrexate and trimethoprim, bind to the active site, preventing the binding of dihydrofolate and NADPH. These inhibitors mimic the structure of dihydrofolate but cannot be reduced to tetrahydrofolate. This competitive inhibition effectively reduces the availability of tetrahydrofolate, impairing DNA synthesis and cell division. These inhibitors are used in treating cancers and bacterial infections, respectively.
