329
Pathway
Fluorouracil Metabolism Pathway
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a fluoropyrimidine anticancer drug. By injection into a vein, it is used to treat colon cancer, esophageal cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. As a cream, it is used for actinic keratosis, basal cell carcinoma, and skin warts. Fluorouracil is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system (Wikipedia). Fluorouracil exerts cytotoxic effects on the cell by direct incorporation into DNA and RNA as well as by inhibiting thymidylate synthase.
Drug Metabolism
PW000584
Center
PathwayVisualizationContext654
560
1100
#000099
PathwayVisualization177
329
Fluorouracil Pathway
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a fluoropyrimidine anticancer drug. By injection into a vein, it is used to treat colon cancer, esophageal cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. As a cream, it is used for actinic keratosis, basal cell carcinoma, and skin warts. Fluorouracil is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system (Wikipedia). Fluorouracil exerts cytotoxic effects on the cell by direct incorporation into DNA and RNA as well as by inhibiting thymidylate synthase.
Drug
1
1521
12724731
Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. doi: 10.1038/nrc1074.
329
Pathway
1522
1707544
Parker WB, Cheng YC: Metabolism and mechanism of action of 5-fluorouracil. Pharmacol Ther. 1990;48(3):381-95.
329
Pathway
1
Cell
CL:0000000
1
Homo sapiens
9606
Eukaryote
Human
1
Cytosol
GO:0005829
15
Nucleus
GO:0005634
5
Cytoplasm
GO:0005737
2
1
1
1
PW_BS000002
23
15
1
1
PW_BS000023
8
5
1
1
PW_BS000008
9039
Fluorouracil
HMDB0014684
Fluorouracil is only found in individuals that have used or taken this drug. It is a pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [PubChem]The precise mechanism of action has not been fully determined, but the main mechanism of fluorouracil is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5–10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex. This results in the inhibition of the formation of thymidylate from uracil, which leads to the inhibition of DNA and RNA synthesis and cell death. Fluorouracil can also be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis.
51-21-8
C07649
3385
46345
3268
DB00544
FC1=CNC(=O)NC1=O
C4H3FN2O2
InChI=1S/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)
GHASVSINZRGABV-UHFFFAOYSA-N
5-fluoro-1,2,3,4-tetrahydropyrimidine-2,4-dione
130.0772
130.017855555
-1.35
2
fluorouracil
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0
DBMET00418
5-fluorouracil;5-fluoracil;5-fluoropyrimidine-2,4-dione;5-fu;Fluorouracilo;Fluorouracilum
PW_C009039
FloUrl
3381
2
3390
23
2411
Thymidylate synthase
P04818
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
HMDBP04363
TYMS
18p11.32
X02308
1
2.1.1.45
2766
2
4316
8
705
Thymidylate synthase
1
PW_P000705
798
2411
1
1753
false
PW_R001753
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6597
9039
1
Compound
false
6598
705
1
ProteinComplex
false
6753
9039
2
157
false
705
170
10
regular
200
190
2879
2411
2
6
false
265
225
8
subunit
regular
160
80
2547
705
177
2
2868
2879
10251
M705 265 C660 265 476 265 427 265
148
false
18
false
true
M 446.87867965644034 196.1507575950825 L 449 211 L 451.12132034355966 225.8492424049175
10252
M427 265 C457 265 163.5 33 187.5 50
5
true
18
2002
177
1753
2
6998
6753
10251
Left
38
2547
10252
Right
460
87
140
135
1.0
1.0
0
2
14
327
267
471
M75 170 C75 120 125 70 175 70 C397 70 684 70 906 70 C956 70 1006 120 1006 170 C1006 230 1006 308 1006 368 C1006 418 956 468 906 468 C684 468 397 468 175 468 C125 468 75 418 75 368 C75 308 75 230 75 170
1
true
6
931.0
398.0