A lipophilic antifolate DHFR inhibitor (Kds = 4.5, 1.4, and 0.1 nM for the bovine, murine, and E. coli enzyme, respectively); has enhanced binding in the presence of NADPH (Kds = 0.03, 0.43, and 0.03 nM, for the bovine, murine, and E. coli enzyme, respectively); inhibits L1210 cell growth (IC50 = 20 nM after two days); halts the cell cycle at the G1/S phase in L1210 mouse lymphocytic leukemia cells at 30 nM; inhibits the growth of S. faecalis and S. aureus (IC50s = P. berghei infection at 0.44 mg/kg per day; increase the median survival time in a mouse model of T. gondii infection at 180 mg/kg; enhances the activity of doxorubicin, cyclophosphamide, and 6-TG in mice with advanced stage P338 leukemia