Fluoropyrimidine activity (WP1601)

Homo sapiens

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]

Authors

Alex Pico , Kristina Hanspers , Anwesha Bohler , Chris Evelo , Egon Willighagen , Aaron Caine , Denise Slenter , Martina Summer-Kutmon , Etaglobin , Friederike Ehrhart , and Eric Weitz

Activity

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Cited In

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Organisms

Homo sapiens

Communities

CPTAC Diseases ExRNA

Annotations

Cell Type Ontology

hepatocyte

Disease Ontology

cancer

Pathway Ontology

cancer pathway drug pathway

Participants

Label Type Compact URI Comment
5-fluorouracil (5-FU) Metabolite chebi:46345
Capecitabine Metabolite chebi:31348
5-dFUR Metabolite wikidata:Q1253473
dTMP Metabolite hmdb:HMDB0001227
FUTP Metabolite pubchem.compound:10255482
FUPA Metabolite pubchem.compound:151244
FdUTP Metabolite pubchem.compound:503023
Tegafur Metabolite chemspider:5193
Leucovorin Metabolite pubchem.compound:135403648
dUMP Metabolite hmdb:HMDB0001409
5-FU Metabolite chebi:46345
FUDP Metabolite pubchem.compound:46936877
FUMP Metabolite cas:796-66-7
FBAL Metabolite pubchem.compound:13351
5,10-Methylenetetrahydrofolate Metabolite chemspider:97272
FdUDP Metabolite pubchem.compound:53882537
Dihydrofolate Metabolite hmdb:HMDB0001056
FUDR Metabolite wikidata:Q5462356
FdUMP Metabolite pubchem.compound:8642
5-dFCR Metabolite pubchem.compound:10037499
DHFU Metabolite pubchem.compound:121997
UPP1 GeneProduct ncbigene:7378
TK1 GeneProduct ncbigene:7083
SLC22A7 GeneProduct ncbigene:10864
ABCC5 GeneProduct ncbigene:10057
DHFR GeneProduct ncbigene:1719
CDA GeneProduct ncbigene:978
TDG GeneProduct ncbigene:6996
ABCC3 GeneProduct ncbigene:8714
UPP2 GeneProduct ncbigene:151531
DPYD GeneProduct ncbigene:1806
MIR29C GeneProduct ensembl:ENSG00000284214
FPGS GeneProduct ncbigene:2356
ABCC4 GeneProduct ncbigene:10257
SMUG1 GeneProduct ncbigene:23583
TYMS GeneProduct ncbigene:7298
TYMP GeneProduct ncbigene:1890
MTHFR GeneProduct ncbigene:4524
DPYS GeneProduct ncbigene:1807
RRM1 GeneProduct ncbigene:6240
UMPS GeneProduct ncbigene:7372
UCK1 GeneProduct ncbigene:83549
XRCC3 GeneProduct ncbigene:7517
ERCC2 GeneProduct ncbigene:2068
CES1 GeneProduct ncbigene:1066
UCK2 GeneProduct ncbigene:7371
GGH GeneProduct ncbigene:8836
CYP2A6 GeneProduct ncbigene:1548
ABCG2 GeneProduct ncbigene:9429
TP53 GeneProduct ncbigene:7157
RRM2 GeneProduct ncbigene:6241
SLC29A1 GeneProduct ncbigene:2030
UPB1 GeneProduct ncbigene:51733
PPAT GeneProduct ncbigene:5471
CES2 GeneProduct ncbigene:8824

References

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