TY - JOUR
T1 - Metabolism of pyrimidine analogues and their nucleosides
AU - Daher, George C.
AU - Harris, Barry E.
AU - Diasio, Robert B.
PY - 1990
Y1 - 1990
N2 - The pyrimidine antimetabolite drugs consist of base and nucleoside analogues of the naturally occurring pyrimidines uracil, thymine and cytosine. As is typical of antimetabolites, these drugs have a strong structural similarity to endogenous nucleic acid precursors. The structural differences are usually substitutions at one of the carbons in the pyrimidine ring itself or substitutions at one of the hydrogens attached to the ring of the pyrimidine or sugar (ribose or deoxyribose). Despite the differences noted above, these analogues, can still be taken up into cells and then metabolized via anabolic or catabolic pathways used by endogenous pyrimidines. Cytotoxicity results when the antimetabolite either is incorporated in place of the naturally pyrimidine metabolite into a key molecule (such as RNA or DNA) or competes with the naturally occurring pyrimidine metabolite for a critical enzyme. There are four pyrimidine antimetabolites that are currently used extensively in clinical oncology. These include the fluoropyrimidines, fluorouracil and fluorodeoxyuridine, and the cytosine analogues, cytosine arabinoside and azacytidine.
AB - The pyrimidine antimetabolite drugs consist of base and nucleoside analogues of the naturally occurring pyrimidines uracil, thymine and cytosine. As is typical of antimetabolites, these drugs have a strong structural similarity to endogenous nucleic acid precursors. The structural differences are usually substitutions at one of the carbons in the pyrimidine ring itself or substitutions at one of the hydrogens attached to the ring of the pyrimidine or sugar (ribose or deoxyribose). Despite the differences noted above, these analogues, can still be taken up into cells and then metabolized via anabolic or catabolic pathways used by endogenous pyrimidines. Cytotoxicity results when the antimetabolite either is incorporated in place of the naturally pyrimidine metabolite into a key molecule (such as RNA or DNA) or competes with the naturally occurring pyrimidine metabolite for a critical enzyme. There are four pyrimidine antimetabolites that are currently used extensively in clinical oncology. These include the fluoropyrimidines, fluorouracil and fluorodeoxyuridine, and the cytosine analogues, cytosine arabinoside and azacytidine.
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U2 - 10.1016/0163-7258(90)90080-L
DO - 10.1016/0163-7258(90)90080-L
M3 - Review article
C2 - 2293239
AN - SCOPUS:0025666730
SN - 0163-7258
VL - 48
SP - 189
EP - 222
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
IS - 2
ER -