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• W2012204523 abstract "The stereoselective transport of methotrexate (L-amethopterin, L-MTX) and its antipode (D-amethopterin, D-MTX) by human reduced folate carrier (hRFC) has been examined in HEK293 cells expressing H27-hRFC and R27-hRFC. The uptake of both L-MTX and D-MTX increased as the extracellular pH increased from 6.0 to 7.4. The initial uptake rate of L-MTX into the H27- and R27-hRFCs of the HEK293 cells followed Michaelis-Menten kinetics with Km values of approximately 0.24 and 0.47 µM, respectively. Dixon plots revealed that the [(3)H]-L-MTX uptake mediated by the H27- and R27-hRFCs was inhibited competitively by unlabeled L-MTX with Ki values of approximately 0.1 and 0.5 µM, respectively. D-MTX also competitively inhibited the H27- and R27-hRFC mediated uptake of [(3)H]-L-MTX with Ki values of approximately 3.4 and 3.2 µM, respectively. The RFC-mediated uptake clearance of L-MTX was approximately 15-fold greater than that of D-MTX in the H27-hRFC-HEK293 cells, and was more than 30-fold greater than that of D-MTX in the R27-hRFC-HEK293 cells. The results of the current study have revealed that the enantiomers of MTX enantiomers can be transported in a stereoselective manner by the H27- and R27-hRFCs because of significant differences in the affinities of the enantiomers to the hRFC." @default.
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• W2012204523 date "2014-01-01" @default.
• W2012204523 modified "2023-09-23" @default.
• W2012204523 title "Stereoselective Transport of Human His27- and Arg27-Reduced Folate Carrier" @default.
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• W2012204523 doi "https://doi.org/10.1248/bpb.b13-00803" @default.
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