By Robert C. Jackson (auth.), Ann L. Jackman (eds.)
In Antifolate medicines in melanoma treatment, Ann Jackman and a panel of very hot researchers comprehensively evaluation the present prestige of novel antifolates, an enormous category of anticancer medications. the celebrated members speak about the preclinical and medical pharmacology of methotrexate, different dihydrofolate reductase inhibitors,
5-fluorouracil, and the recent iteration of antifolates-the thymidylate synthase and glycinamide ribonucleotide formyltransferase inhibitors. moreover, they assessment intensive the modulation of antifolate medications, folate and antifolate delivery mechanisms, polyglutamation, resistance, and drug combos, in addition to pharmacogenomics, pharmacodynamics, rules of gene expression, and mechanisms of mobile demise.
The huge and innovative scope of Antifolate medicines in melanoma treatment presents entré to fascinating new avenues for destiny examine, and constitutes a brand new general reference for all easy scientists and clinicians engaged in melanoma therapeutics.
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Extra resources for Antifolate Drugs in Cancer Therapy
Stover, and C. Wagner. REFERENCES 1. Farber S, Diamond LK, Mercer RD, Sylvester RF, Jr, Wolff JA. Temporary remissions in acute leukemia in children produced by folie acid antagonist, 4-aminopteroyl-glutamic acid (arninopterin) New Engl J Med 1948;238:787-793. 2. ). Folates and Pterins, vol. 1, John Wiley & Sons, NY, 1984. 3. Kisliuk RL. The biochemistry of folates, in Sirotnak FM, Burehall JJ, Ensminger WD, Montgomery JA, eds. Folate Antagonists as Therapeutic Agents. voll Academic Press, Orlando, 1984, pp.
In the absence of H4 PteGlun or if the folate site is blocked chemically, both enzymes continue to oxidize methyl groups unabated, yielding free formaldehyde stoichiometrically (114,115). Dimethylglycine dehydrogenase from rat liver and from rabbit liver bind both ~PteGlul and H4 PteGIus very tightly with K d values < 1 ~ (44,115). Rat liver dimethylglycine dehydrogenase has been c10ned (116). The enzyme is present in highest amounts in liver and kidney, but low levels are found in many tissues (117).
10. FORMIMINOTRANSFERASE-CYCLODEAMINASE The two activities of this protein serve to catalyze the conversion of the formimino group, arising as formiminoglutamic acid in histidine catabolism, to formimino H4 PteGlun and then to 5,1O-CH-H4 PteGlun. The porcine enzyme has been cloned, sequenced, and expressed (106). It is a 480-kDa tetramer of dimers that channels formiminoH 4PteGlu5 between the formiminotransferase and cyclodeaminase sites. Both activities require the formation of specific subunit interfaces (107).