NSC 131463

NSC 131463 is a dihydrofolate reductase potent inhibitor with an IC50 of 1 nM. It is a minor metabolite of methotrexate. It inhibited L1210 cell proliferation in culture (IC50 = 0.3 uM), and prolonged the survival of L1210 leukemic mice (98% increase in lifespan at 120 mg/kg, qdx9). Studies on the interaction of mAPA-HCysA with partially purified mouse liver folyl polyglutamate synthetase revealed that mAPA-HCysA was not a substrate. Hence, the increased dose of mAPA-HCysA required to inhibit tumor growth in vitro and in vivo relative to methotrexate may reflect, in part, the inability of this compound to form non-effluxing polyglutamates.