5-Monobutyl methotrexate (NSC 305986; γ-MBMTX) is a dihydrofolate reductase ( DHFR ) inhibitor and esterase substrate. 5-Monobutyl methotrexate is hydrolyzed by esterases to produce methotrexate. In rhesus monkeys, 5-Monobutyl methotrexate clears more slowly from cerebrospinal fluid than from serum, and its serum protein binding rate exceeds 99%. At the same dose rate, 5-Monobutyl methotrexate achieves cerebrospinal fluid concentrations comparable to those of Methotrexate ( HY-14519 ), and exhibits activity against Methotrexate -resistant cells (with transport defects) that is comparable to that against sensitive parental cells. 5-Monobutyl methotrexate can be used in studies related to Methotrexate -resistant tumors.
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