Methotrexate (MTX) was conjugated to an immunoglobulin G1 (IgG1) monoclonal antibody specific for human prostatic acid phosphatase (PAP) by the active ester method. The molar ratio of MTX to IgG was 14. MTX-monoclonal antibody conjugate retained substantially the original PAP-binding inhibition activity of the monoclonal antibody. Both MTX-monoclonal antibody conjugate and an identically prepar...

The antifolate compound methotrexate (MTX) is toxic to the gram-positive bacterium Streptococcus pneumoniae. Interaction of MTX with this bacterium resulted in an increase in the electric transmembrane potential (delta psi) and enhanced the delta psi-dependent uptake of isoleucine and MTX. In contrast, delta psi-independent uptake of glutamine was not changed. Folate, a nontoxic analog of MTX, ...

Bile, urine, and serum concentrations of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) were monitored in rats in vivo following a short-time infusion of 10 mg/kg [3H]MTX. The experiments were performed in one group of anesthetized, bile-drained rats and in two control groups, one anesthetized and one unanesthetized, that were not bile-drained. Peak biliary levels of MTX (3.8 x 10(-3)...

Studies were undertaken to characterize the cellular pharmacology of 7-hydroxymethotrexate (7-OH-MTX) in Ehrlich ascites tumor cells, compare it to that of methotrexate (MTX), and define the interactions between the parent compound and its catabolite. Transport of 7-OH-MTX is mediated by the MTX-tetrahydrofolate cofactor carrier, with a Km of 9 microM in comparison to the MTX Km of 5 microM. Bo...

Methotrexate (MTX), i.e., MTX-polygluatmate 1 (MTX-PG(1)), exerts its antirheumatic effects mainly by < or = 6 (MTX-PG(2-7)) via folypolyglutamyl synthase in cells. The authors developed a new method using fluorescence polarization immunoassay to determine MTX-PG(1-7) concentrations in erythrocytes (RBC). MTX-PG(2-7) in RBC of rheumatoid arthritis (RA) patients receiving MTX was converted to MT...

Stereoselective transport of methotrexate (L-amethopterin, L-MTX) and its antipode (D-amethopterin, D-MTX) by the proton-coupled folate transporter (PCFT) was examined using PCFT-expressing HEK293 cells (PCFT-HEK293 cells). Uptake of both L-MTX and D-MTX was pH-dependent and decreased with an increase in the extracellular pH from 5.0 to 7.4. The initial uptake rate of L-MTX into PCFT-HEK293 cel...

a new sensitive, simple and rapid method for determination of methotrexate (mtx) was developed based on quenching effects of mtx on the fluorescence intensity of tb3+-1,10-phenanthroline complex. the fluorescence intensity was measured with excitation wavelength of 300 nm and emission wavelength of 545 nm and the quenched fluorescence intensity is proportional to the concentration of mtx in tris...

BACKGROUND Methotrexate (MTX), one of the main drugs used to treat osteosarcoma, is a representative folic acid antagonist. Polymorphisms of various enzymes involved in the metabolism of MTX could contribute to differences in response to MTX in pediatric osteosarcoma patients. METHODS Blood and tissue samples were obtained from 37 pediatric osteosarcoma patients who were treated with high-dos...

To identify the major factors predicting the response to Methotrexate (MTX) therapy in rheumatoid arthritis (RA) patients, we evaluated the relationship between the response to MTX and factors such as the concentration of MTX-polyglutamates (MTX-PGs) in erythrocytes (RBCs), genotypes of thymidylate synthase (TYMS) 5'-UTR (2R/3R) and 3'-UTR (-6/+6), 5,10-methylenetetrahydrofolate reductase (MTHF...

Generation 5 poly(amidoamine) (G5 PAMAM) methotrexate (MTX) conjugates employing two small molecular linkers, G5-(COG-MTX)n, G5-(MFCO-MTX)n were prepared along with the conjugates of the G5-G5 (D) dimer, D-(COG-MTX)n, D-(MFCO-MTX)n. The monomer G5-(COG-MTX)n conjugates exhibited only a weak, rapidly reversible binding to folate binding protein (FBP) consistent with monovalent MTX binding. The D...