Biochem/physiol Actions
LY345899 (LY354899) is a methylenetetrahydrofolate dehydrogenase inhibitor (MTHFD1 IC50 = 96 nM with 30 μM folitixorin and 400 μM NADP+; MTHFD2 IC50 = 663 nM with 5 μM folitixorin and 250 μM NAD+) that exerts antiproliferation activity against cancer cells by targeting the folate cycle. Co-administer LY345899 with the dihydrofolate reductase (DHFR) inhibitor methotrexate (MTX) overcomes AML MTX resistance (50 mg/kg) in mice in vivo (10 mg/kg q.o.d. i.p.).
Methylenetetrahydrofolate dehydrogenase 1/2 (MTHFD1/2) inhibitor that exerts anti-cancer efficacy in vitro and in vivo by targeting the folate cycle.