Fluoropyrimidine activity (WP1601)

The main mechanism of 5-FU activation is conversion to fluorodeoxyuridine monophosphate (FdUMP) which inhibits the enzyme thymidylate synthase (TYMS), an important part of the folate-homocysteine cycle and purine and pyrimidine synthesis The conversion of 5-FU to FdUMP can occur via thymidylate phosphorylase (TYMP) to fluorodeoxyuridine (FUDR) and then by the action of thymidine kinase to FdUMP or indirectly via fluorouridine monophosphate (FUMP) or fluroridine (FUR) to fluorouridine diphosphate (FUDP) and then ribonucleotide reductase action to FdUDP and FdUMP. FUDP and FdUDP can also be converted to FUTP and FdUTP and incorporated into RNA and DNA respectively which also contributes to the pharmacodynamic actions of fluoropyrimidines. Sources: [https://www.pharmgkb.org/pathway/PA150653776 PharmGKB:Fluoropyrimidine Pharmacokinetics], [https://www.pharmgkb.org/pathway/PA165291507 PharmGKB:Fluoropyrimidine Pharmacodynamics], [http://en.wikipedia.org/wiki/Fluorouracil Wikipedia:Fluorouracil] Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP1601 CPTAC Assay Portal]
last edited

Authors

AlexanderPico, MaintBot, Khanspers, Anwesha, Evelo, Egonw, AaronCaine, DeSl, Mkutmon, Etaglobin, Fehrhart, and Eweitz

Cited In

Organism

Homo sapiens

Communities

CPTAC Diseases

Annotations

Pathway Ontology: drug pathway cancer pathway

Disease Ontology: cancer

Cell Type Ontology: hepatocyte

Participants

Label Type Compact Identifier
5-fluorouracil (5-FU) Metabolite chebi:46345
Capecitabine Metabolite chebi:31348
FUR Metabolite None
5-dFUR Metabolite wikidata:Q1253473
dTMP Metabolite hmdb:HMDB0001227
FUTP Metabolite pubchem.compound:10255482
FUPA Metabolite pubchem.compound:151244
FdUTP Metabolite pubchem.compound:503023
UPP1 GeneProduct ncbigene:7378
TK1 GeneProduct ncbigene:7083
5-hydroxytegafur Metabolite None
SLC22A7 GeneProduct ncbigene:10864
ABCC5 GeneProduct ncbigene:10057
DHFR GeneProduct ncbigene:1719
CDA GeneProduct ncbigene:978
TDG GeneProduct ncbigene:6996
Tegafur Metabolite chemspider:5193
Leucovorin Metabolite pubchem.compound:135403648
ABCC3 GeneProduct ncbigene:8714
UPP2 GeneProduct ncbigene:151531
DPYD GeneProduct ncbigene:1806
MIR29C GeneProduct ensembl:ENSG00000284214
UPP1 GeneProduct ncbigene:7378
FPGS GeneProduct ncbigene:2356
ABCC4 GeneProduct ncbigene:10257
SMUG1 GeneProduct ncbigene:23583
TYMS GeneProduct ncbigene:7298
TYMP GeneProduct ncbigene:1890
MTHFR GeneProduct ncbigene:4524
dUMP Metabolite hmdb:HMDB0001409
DPYS GeneProduct ncbigene:1807
RRM1 GeneProduct ncbigene:6240
UMPS GeneProduct ncbigene:7372
DNA Repair Pathway wikipathways:WP1805
5-FU Metabolite chebi:46345
FUDP Metabolite pubchem.compound:46936877
UCK1 GeneProduct ncbigene:83549
XRCC3 GeneProduct ncbigene:7517
FUMP Metabolite cas:796-66-7
ERCC2 GeneProduct ncbigene:2068
Folate Cycle Pathway wikipathways:WP176
CES1 GeneProduct ncbigene:1066
UCK2 GeneProduct ncbigene:7371
5-FU Metabolite chebi:46345
FBAL Metabolite pubchem.compound:13351
FUTP Metabolite pubchem.compound:10255482
5,10-Methylenetetrahydrofolate Metabolite chemspider:97272
FdUTP Metabolite pubchem.compound:503023
GGH GeneProduct ncbigene:8836
CYP2A6 GeneProduct ncbigene:1548
FdUDP Metabolite pubchem.compound:53882537
ABCG2 GeneProduct ncbigene:9429
5-FU Metabolite chebi:46345
Dihydrofolate Metabolite hmdb:HMDB0001056
TP53 GeneProduct ncbigene:7157
RRM2 GeneProduct ncbigene:6241
Apoptosis Pathway wikipathways:WP254
FUDR Metabolite wikidata:Q5462356
FdUMP Metabolite pubchem.compound:8642
FdUMP Metabolite pubchem.compound:8642
5-dFCR Metabolite pubchem.compound:10037499
SLC29A1 GeneProduct ncbigene:2030
UPB1 GeneProduct ncbigene:51733
UPP2 GeneProduct ncbigene:151531
TYMP GeneProduct ncbigene:1890
PPAT GeneProduct ncbigene:5471
ABCC4 GeneProduct ncbigene:10257
DHFU Metabolite pubchem.compound:121997
CES2 GeneProduct ncbigene:8824

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