Fig. 2: Substrates and Inhibitors of DHFR.

a Dihydrofolate reductase (DHFR) converts dihydrofolate (DHF) to tetrahydrofolate (THF) by protonation form solvent and hydride transfer from NADPH. b The structures of clinically relevant DHFR inhibitors and propargyl-linked antifolates, UCP1223 and UCP1228.