Dihydrofolate Reductase catalyzes the reduction of dihydrofolate to tetrahydrofolate using NADPH as the electron donor. Tetrahydrofolate is essential as a cofactor for several enzymes responsible for the synthesis of purines, thymidylic acid, and some amino acids, making DHFR indispensable for DNA synthesis and cell proliferation. DHFR is present in most tissues and cells with activity peaking at the G1/S boundary. In humans, there are two genes: DHFR and DHFR2/DHFRL1, with the latter targeted to mitochondria. Interestingly, mammalian DHFR can also reduce folic acid to THF, allowing for the use of folic acid in food supplementation. DHFR inhibitors are used in several therapeutic interventions, including cancer treatment (methotrexate), antibiotics (trimethoprim) and antiparasitic drugs (pyrimethamine). Due to the difference between mammalian DHFR and DHFR from other species, selective inhibitors can be developed. AkrivisBio’s Dihydrofolate Reductase Inhibitor Screening Kit allows for quantitative assessment of decreases in DHFR activity in the presence of candidate compounds.
