Information on EC 2.4.2.4 - thymidine phosphorylase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
2.4.2.4
-
RECOMMENDED NAME
GeneOntology No.
thymidine phosphorylase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
mechanism
-
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
mechanism
-
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
rapid equilibrium random bi-bi mechanism with an enzyme-phosphate-thymine dead-end complex
-
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
ordered sequential reaction mechanism, phosphate is the first substrate to bind to and deoxyribose the last product to dissociate from the enzyme
-
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
ordered bi bi mechanism with the nucleoside the first substrate to add, and the pyrimidine base the last product to leave
-
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
SN2-type catalytic mechanism
-
thymidine + phosphate = thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
ordered bi bi mechanism with the nucleoside the first substrate to add, and the pyrimidine base the last product to leave
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pentosyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Drug metabolism - other enzymes
-
-
Metabolic pathways
-
-
pyrimidine deoxyribonucleosides degradation
-
-
Pyrimidine metabolism
-
-
pyrimidine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
thymidine:phosphate deoxy-alpha-D-ribosyltransferase
The enzyme in some tissues also catalyses deoxyribosyltransferase reactions of the type catalysed by EC 2.4.2.6, nucleoside deoxyribosyltransferase.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
animal growth regulators, blood platelet-derived endothelial cell growth factors
-
-
-
-
blood platelet-derived endothelial cell growth factor
-
-
-
-
deoxythymidine phosphorylase
-
-
-
-
dthdpase
-
-
-
-
gliostatin
-
-
-
-
gliostatins
-
-
-
-
PD-ECGF
-
-
-
-
PD-ECGF/TP platelet-derived endothelial cell growth factor
-
-
-
-
phosphorylase, thymidine
-
-
-
-
pyrimidine deoxynucleoside phosphorylase
-
-
-
-
pyrimidine phosphorylase
-
-
-
-
TDRPASE
-
-
-
-
thymidine-orthophosphate deoxyribosyltransferase
-
-
-
-
thymidine:orthophosphate deoxy-D-ribosyltransferase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9030-23-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
recombinant
-
-
Manually annotated by BRENDA team
strain B
-
-
Manually annotated by BRENDA team
strain W, ATCC 9637
-
-
Manually annotated by BRENDA team
Escherichia coli K12
K12
-
-
Manually annotated by BRENDA team
normal and tumor tissue
-
-
Manually annotated by BRENDA team
recombinant enyzme
-
-
Manually annotated by BRENDA team
C57Bl6/J mice
-
-
Manually annotated by BRENDA team
Mus musculus C57Bl6/J
C57Bl6/J mice
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
LT-2
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
a loss-of-function mutation is involved in mitochondrial neurogastrointestinal encephalomyopathy, an autosomal recessive human disorder associated with multiple deletions of skeletal muscle mitochondrial DNA, overview. Corrleation of tumor development and progression with intratumoral thymidine phsophorylase levels, overview
malfunction
-
deficiency of the cytosolic enzyme thymidine phosphorylase causes a multisystem disorder called mitochondrial neurogastrointestinal encephalomyopathy syndrome with symptoms gastrointestinal dysfunction, muscle involvement and neurological deterioration, overview
malfunction
-
thymidine phosphorylase promotes angiogenesis. The mechanism of endometrial angiogenesis involves the enzyme and stimulation by ovarian steroids of production of angiogenic regulators by endometrial epithelium and stroma which then act on the endothelium
metabolism
-
the enzyme is involved in the thymidine salvage pathway and competes with thymidine kinase, overview. Thymidine plays a central role in both proliferation and angiogensis, overview
metabolism
-
the enzyme is the key enzyme of the pyrimidine salvage pathway
metabolism
-
the enzyme participates in the thymidine salvage pathway maintaining the thymidine pool in the cell
metabolism
-
the enzyme plays a key role in nucleoside metabolism
physiological function
-
2-deoxy-D-ribose, a downstream mediator of thymidine phosphorylase, regulates tumor angiogenesis and progression, mechanism, overview
physiological function
-
heterogeneous nuclear ribonucleoprotein K and thymidine phosphorylase prevent hypoxia-induced apoptosis in nasopharyngeal carcinoma cells, overview
physiological function
-
the enzyme is the sole endothelial mitogenic and angiogenic factor, it plays a role in the stimulation of chemotaxis and thymidine incorporation into endothelial cells in vitro and angiogenesis in vivo
physiological function
-
the enzyme plays an important role in the female reproductive cycle, and is also involved in a wide variety of chronic inflammatory diseases. Dual role of thymidine phosphorylase in cancer development and chemotherapy, acts as thymidine salvage enzyme and as platelet-derived endothelial cell growth factor inducing endothelial cell migration in vitro and angiogenesis in vivo, overview. The enzyme promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis. The enzyme is also indispensable for the activation of the extensively used 5-fluorouracil prodrug capecitabine. Role of thymidine phosphorylase in angiogenesis, mediators are matrix metalloproteinases, interleukin-8, P-selectin, and vascular epithelial growth factor, detailed overview
physiological function
-
the enzyme promotes the survival and neurite outgrowth of cortical neurons
physiological function
-
thymidine phosphorylase is a key regulator of the angiogenic potential of colony-forming units and endothelial progenitor cell cultures, overview. The enzyme is a survival factor, it protects against apoptosis, stimulates endothelial cell migration and enhances wound healing in vitro and angiogenesis in vivo, overview
physiological function
-
thymidine phosphorylase inhibits vascular smooth muscle cell proliferation via upregulation of STAT3. Overexpression of thymidine phosphorylase increases STAT3 phosphorylation and expression in vascular smooth muscle cells via Lyn. STAT3 protein but not STAT3 phosphorylation is necessary for thymidine phosphorylase inhibited vascular smooth muscle cell proliferation
physiological function
-
transient decrease of mRNA and protein expression by 87.1% and 72.5%, respectively, using siRNAleads to significant decrease in migration of KKU-M139 cells, and suppresses migration and tube formation of human umbilical vein endothelial cells. siRNA also reduces the ability of thymidine phosphorylase to resist hypoxia-induced apoptosis, while suppression of thymidine phosphorylase reduces the sensitivity of KKU-M139 cells to 5-fluorouracil
metabolism
-
thymidine phosphorylase is a catabolic enzyme in thymidine metabolism
additional information
-
elevated enzyme levels are associated with tumor angiogenesis, metastasis and poor prognosis
additional information
-
the cytoplasmic level of heterogeneous nuclear ribonucleoprotein K is significantly correlated with the elevated expression of thymidine phosphorylase, and high levels of both proteins are predictive of a poor prognosis in nasopharyngeal carcinoma
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-(2',6'-dideoxy-alpha-L-lyxo-hexafuranosyl)thymine + phosphate
?
show the reaction diagram
-
-
-
-
?
1-(2',6'-dideoxy-alpha-L-lyxohexafuranosyl)thymine + phosphate
thymine + 2,6-dideoxy-L-lyxohexafuranose 1-phosphate
show the reaction diagram
-
-
-
-
?
1-(2',6'-dideoxy-beta-D-ribo-hexafuranosyl)thymine + phosphate
?
show the reaction diagram
-
-
-
-
?
1-(2',6'-dideoxy-beta-D-ribohexafuranosyl)thymine + phosphate
?
show the reaction diagram
-
-
-
-
?
1-(2',6'-dideoxy-beta-D-ribohexafuranosyl)thymine + phosphate
thymine + 2,6-dideoxy-D-ribohexafuranose 1-phosphate
show the reaction diagram
-
-
-
-
?
1-(tetrahydro-2-furanyl)-5-fluorouracil + phosphate
?
show the reaction diagram
-
i.e. Tegafur
-
-
-
1-(tetrahydro-2-furanyl)-5-fluorouracil + phosphate
?
show the reaction diagram
-
i.e. Tegafur
-
-
?
1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione + phosphate
?
show the reaction diagram
-
56% conversion after one h
-
-
?
1-[(2R,4S,5R)-5-(aminomethyl)-4-hydroxytetrahydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione + phosphate
?
show the reaction diagram
-
11% conversion after one h
-
-
?
1-[(2R,4S,5R)-5-(hydroxymethyl)-4-sulfanyltetrahydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione + phosphate
?
show the reaction diagram
-
0.76% conversion after one h
-
-
?
1-[(2R,4S,5S)-4-hydroxy-5-(sulfanylmethyl)tetrahydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione + phosphate
?
show the reaction diagram
-
39% conversion after one h
-
-
?
1-[(2R,4S,5S)-5-(chloromethyl)-4-hydroxytetrahydrofuran-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione + phosphate
?
show the reaction diagram
-
24% conversion after one h
-
-
?
2'-deoxy-5-nitrouridine + phosphate
5-nitrouracil + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxythymidine + phosphate
thymidine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
2'-deoxythymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
P07650
-
-
-
?
2'-deoxyuridine + phosphate
?
show the reaction diagram
-
-
-
-
?
3'-amino-3'-deoxythymidine + phosphate
?
show the reaction diagram
-
at pH 8.0
-
-
?
3'-deoxy-2',3'-didehydrothymidine + phosphate
?
show the reaction diagram
-
-
-
-
?
3'-deoxy-2',3'-didehydrothymidine + phosphate
thymine + 2,3-dideoxy-2,3-didehydro-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
3'-deoxythymidine + phosphate
thymine + 2,3-dideoxy-D-ribose 1-phosphate
show the reaction diagram
-
3.2% conversion after one h
-
-
?
3'-thiothymidine + phosphate
thymine + 3-thio-2,3-dideoxy-D-ribose 1-phosphate
show the reaction diagram
-
0.76% conversion after 1 h
-
-
?
3-fluorothymidine + phosphate
3-fluorothymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
4'-thiothymidine + phosphate
?
show the reaction diagram
-
3.8% conversion after one h
-
-
?
4-thiothymidine + phosphate
4-thiothymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
4-thiothymidine + phosphate
?
show the reaction diagram
-
-
-
-
?
5'-amino-5'-deoxythymidine + phosphate
?
show the reaction diagram
-
-
-
-
?
5'-amino-5'-deoxythymidine + phosphate
thymine + 2,5-dideoxy-5-amino-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-amino-5'-deoxythymidine + phosphate
thymine + 5-amino-2,5-dideoxy-D-ribose 1-phosphate
show the reaction diagram
-
11% conversion after 1 h
-
-
?
5'-chloro-5'-deoxythymidine + phosphate
?
show the reaction diagram
-
-
-
-
?
5'-chloro-5'-deoxythymidine + phosphate
thymine + 5-chloro-2,5-dideoxy-D-ribose 1-phosphate
show the reaction diagram
-
24% conversion after 1 h
-
-
?
5'-deoxy-5'-fluorothymidine + phosphate
thymine + 5-fluoro-2,5-dideoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxyribose-1-phosphate
show the reaction diagram
-
-
-
-
-
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxyribose-1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxyribose-1-phosphate
show the reaction diagram
-
5'-DFUR
-
-
?
5'-deoxy-5-fluorouridine + phosphate
5-fluorouracil + 5-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxythymidine + phosphate
?
show the reaction diagram
-
-
-
-
?
5'-deoxythymidine + phosphate
thymine + 2,5-dideoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5'-deoxythymidine + phosphate
thymine + 2,5-dideoxy-D-ribose 1-phosphate
show the reaction diagram
-
68% conversion after one h
-
-
?
5'-thiothymidine + phosphate
thymine + 5-thio-2,5-dideoxy-D-ribose 1-phosphate
show the reaction diagram
-
39% conversion after 1 h
-
-
?
5-deoxythymidine + phosphate
thymine + 2,5-dideoxyribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxyribose-1-phosphate
show the reaction diagram
-
-
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxyribose-1-phosphate
show the reaction diagram
-
-
-
?
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxyribose-1-phosphate
show the reaction diagram
-
-
-
-
r
5-fluoro-2'-deoxyuridine + phosphate
5-fluorouracil + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-fluorouracil + 2-deoxy-alpha-D-ribose 1-phosphate
5-fluoro-2'-deoxyuridine + phosphate
show the reaction diagram
-
the enzyme converts 5-fluorouracil to 5-fluoro-2'-deoxyuridine, activating the prodrug, overview. This action can only take place if there is enough co-substrate. 5-Fluorouracil prodrugs and metabolism, detailed overview
5-fluoro-2'-deoxyuridine is further converted by thymidine kinase to 5-fluoro-2'-deoxyuridine 5'-monophosphate
-
?
5-fluorouracil + 2-deoxy-alpha-D-ribose 1-phosphate
5-fluoro-2'-deoxyuridine + phosphate
show the reaction diagram
-
the enzyme converts 5-fluorouracil to 5-fluoro-2'-deoxyuridine, activating the prodrug, overview. This action can only take place if there is enough co-substrate
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-fluorouridine + phosphate
5-fluorouracil + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-nitro-2'-deoxyuridine + phosphate
5-nitrouracil + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-nitro-2'-deoxyuridine + phosphate
5-nitrouracil + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-nitro-2'-deoxyuridine + phosphate
5-nitrouridine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
5-nitro-2'-deoxyuridine + phosphate
5-nitrouridine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
P19971
-
-
-
?
5-nitro-2'-deoxyuridine + phosphate
5-nitrouridine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
6-azathymidine + phosphate
uracil + deoxyribose-1-phosphate
show the reaction diagram
-
5.4% conversion after one h
-
-
?
bromodeoxyuridine + phosphate
bromouracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
bromodeoxyuridine + phosphate
bromouracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
bromodeoxyuridine + phosphate
bromouracil + 2-deoxy-D-ribose
show the reaction diagram
-
at 40% the rate of thymidine
-
-
?
deoxythymidine + phosphate
thymidine + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
deoxythymidine + phosphate
thymidine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
deoxyuridine + phosphate
uracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
deoxyuridine + phosphate
uracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
deoxyuridine + phosphate
uracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
r
deoxyuridine + phosphate
uracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
deoxyuridine + phosphate
uracil + 2-deoxy-D-ribose
show the reaction diagram
-
1.2-1.4 times the rate of thymidine at pH 5.7
-
-
?
deoxyuridine + phosphate
uracil + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
fluorodeoxyuridine + phosphate
fluorouracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
iododeoxyuridine + phosphate
iodouracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
thymidine + arsenate
?
show the reaction diagram
-
-
-
-
?
thymidine + arsenate
?
show the reaction diagram
-
-
-
-
?
thymidine + arsenate
?
show the reaction diagram
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
-
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
ir
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
in the reverse reaction only alpha-D-2-deoxyribose 1-phosphate is accepted as substrate
-
r
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
enzyme is enantioselective, acts only on the naturally occurring D-thymidine and some D-thymidine analogs, but not on their L-counterparts
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
intact platelets degrade thymidine but are not able to synthesize thymidine from thymine
-
-
-
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
the enzyme confers resistance to apoptosis induced by hypoxia. The enzymatic degradation of thymidine by thymidine phosphorylase is required for the inhibition of hypoxia-induced apoptosis. The enzyme can confer resistance to apoptosis in addition to its angiogenic activity. The enzyme must play some role in the development or malignancy of tumors. Involved in invasion and metastasis of some solid tumors
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
the enzyme plays a crucial role in intratumoral angiogenesis, which occurs in the early phase of ovarian cancer, or influences angiogenesis indirectly
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
P07650
SN1 mechanism for the phosphorolysis reaction, relevant interaction between the His85 imidazole ring and the O2 of thymidine suggesting that this highly conserved residue could play an important role in the catalytic mechanism of TPase
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
86% conversion after one h
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
-
-
?
thymidine + phosphate
thymine + alpha-D-deoxyribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
2-deoxy-alpha-D-ribose 1-phosphate strongly promoted neovascularization
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
Asp203 plays an important role for loop stabilization required for efficient enzyme catalysis
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
Asp203 plays an important role to afford the substrate-binding site loop stabilization that is required for efficient enzyme catalysis
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
substrate binding induces domain movement, which leads to the closed conformation of the active site and initiates phosphorylation, molecular dynamic simulation, overview
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
the enzyme catalyzes the reversible cleavage of the glycosidic bond of pyrimidine 2'-deoxynucleotides, most likely through SN2-like transition state involving nucleobase, 2'-deoxyribose and phosphate. The active site consists of residues His116, Ser117, Leu148, Arg202, Val208, Ile214, Lys221 and Val241
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
Mus musculus C57Bl6/J
-
-
-
-
r
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
-
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
-
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
enzyme is enantioselective, acts only on the naturally occurring D-thymidine and some D-thymidine analogs, but not on their L-counterparts
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
in Escherichia coli and Salmonella typhimurium thymidine phosphorylase plays an important role in metabolism of thymine auxotrophs and is necessary for the conversion of exogenous thymine to thymidine
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
enzyme also catalyzes the nucleoside deoxyribosyltransferase reaction with pyrimidine deoxyribonucleosides, ec2.4.2.6
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
degradation of uridine in tumor specimen
-
-
-
thymine arabinoside + phosphate
thymine + arabinose 1-phosphate
show the reaction diagram
-
-
-
-
?
uracil + phosphate
uracil + ribose 1-phosphate
show the reaction diagram
-
88% conversion after one h
-
-
?
uridine + phosphate
uracil + ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + ribose 1-phosphate
show the reaction diagram
-
-
-
?
uridine + phosphate
uracil + ribose 1-phosphate
show the reaction diagram
-
the activities of uridine, deoxyuridine and thymidine phosphorylases from Giardia lamblia remain associated throughout purification, suggesting that a single enzyme is responsible for the 3 activities
-
-
?
uridine + phosphate
uracil + D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
uridine + phosphate
uracil + D-ribose 1-phosphate
show the reaction diagram
-
56% conversion after 1 h
-
-
?
iododeoxyuridine + phosphate
iodouracil + 2-deoxy-D-ribose
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
no substrate: deoxycytidine
-
-
-
additional information
?
-
-
no substrate: deoxycytidine
-
-
-
additional information
?
-
-
no substrate: deoxycytidine
-
-
-
additional information
?
-
-
no substrates: deoxyadenosine, deoxyguanosine
-
-
-
additional information
?
-
-
specific for deoxyribonucleosides
-
-
-
additional information
?
-
-
specific for deoxyribonucleosides
-
-
-
additional information
?
-
-
the phosphorolytic acitvities towards thymidine, 5'-deoxy-5-fluorouridine and 1-(tetrahydro-2-furanyl)-5-fluorouracil remain closely parallel during purification
-
-
-
additional information
?
-
-
purine deoxyribonucleosides are no substrates
-
-
-
additional information
?
-
-
specificity towards the deoxyribosyl moiety of the substrate
-
-
-
additional information
?
-
-
the enzyme in some tissues also catalyzes deoxyribonucleosyltransferase reaction of the type catalyzed by EC 2.4.2.6: 2-deoxy-D-ribosyl-base1 + base2 = 2-deoxy-D-ribosyl-base2 + base1
-
-
-
additional information
?
-
-
the enzyme in some tissues also catalyzes deoxyribonucleosyltransferase reaction of the type catalyzed by EC 2.4.2.6: 2-deoxy-D-ribosyl-base1 + base2 = 2-deoxy-D-ribosyl-base2 + base1
-
-
-
additional information
?
-
-
the enzyme in some tissues also catalyzes deoxyribonucleosyltransferase reaction of the type catalyzed by EC 2.4.2.6: 2-deoxy-D-ribosyl-base1 + base2 = 2-deoxy-D-ribosyl-base2 + base1
-
-
-
additional information
?
-
-
the enzyme in some tissues also catalyzes deoxyribonucleosyltransferase reaction of the type catalyzed by EC 2.4.2.6: 2-deoxy-D-ribosyl-base1 + base2 = 2-deoxy-D-ribosyl-base2 + base1
-
-
-
additional information
?
-
-
the enzyme in some tissues also catalyzes deoxyribonucleosyltransferase reaction of the type catalyzed by EC 2.4.2.6: 2-deoxy-D-ribosyl-base1 + base2 = 2-deoxy-D-ribosyl-base2 + base1
-
-
-
additional information
?
-
-
the enzyme in some tissues also catalyzes deoxyribonucleosyltransferase reaction of the type catalyzed by EC 2.4.2.6: 2-deoxy-D-ribosyl-base1 + base2 = 2-deoxy-D-ribosyl-base2 + base1
-
-
-
additional information
?
-
-
nonsubstituted pyrimidine moiety or one which is substituted in position 5 required
-
-
-
additional information
?
-
-
purine deoxyribonucleosides and ribonucleosides are not cleaved
-
-
-
additional information
?
-
-
role in thymidine metabolism, homeostasis, development and regeneration of central nervous system and formation of blood/brain barrier
-
-
-
additional information
?
-
-
formation of blood/brain barrier and repair following brain injury
-
-
-
additional information
?
-
-
identical to platelet-derived endothelial cell growth factor
-
-
-
additional information
?
-
-
mitogenic effect, promotes endothelial cell proliferation
-
-
-
additional information
?
-
-
angiogenic activity
-
-
-
additional information
?
-
-
expression of PD-ECGF/TP may play an important role in the progression of solid tumors
-
-
-
additional information
?
-
-
important role in nucleoside metabolism, implicated in angiogenesis and apoptosis
-
-
-
additional information
?
-
-
thymidine phosphorylase and uridine phosphorylase contribute in the conversion of 5'-deoxy-5-fluorouridine into 5-fluorouracil and the conversion of 5-fluorouracil into its active metabolites in peripheral blood mononuclear cell, but thymidine phosphorylase seems to be the most important enzyme for these reactions in PBMC
-
-
-
additional information
?
-
-
molecular modeling based on an X-ray structure of human TP indicates that TP is likely to be mechanistically similar to all other natural members of the class in proceeding through a a oxacarbenium-like transition state or states
-
-
-
additional information
?
-
-
3'-amino-3'-deoxythymidine is not a thymidine phosphorylase substrate at pH 6.5, no activity with uridine and methyluridine
-
-
-
additional information
?
-
-
no activity with 3'beta-thymidine, 4'-thio-1'-alpha-thymidine, 1-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]thymine, 5-methyl-2-pyrimidinone nucleoside, and deoxycytidine
-
-
-
additional information
?
-
-
the enzyme stimulates formation of focal adhesions and the phosphorylation of Tyr397 of focal adhesion kinase, and it induces the expression and/or secretion of other angiogenic factors, overview. Thymidine phosphorylase promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis, detailed overview. As gliostatin from fibroma cells, the enzyme inhibits the growth of both astrocytes and glial tumor cells
-
-
-
additional information
?
-
-
thymidine phosphorylase is identical with platelet-derived endothelial cell growth factor, PD-ECGF, which promotes angiogenesis. The mechanism of endometrial angiogenesis involves thymidine phosphorylase and stimulation by ovarian steroids of production of angiogenic regulators by endometrial epithelium and stroma which then act on the endothelium
-
-
-
additional information
?
-
-
closing/opening motion in the presence of substrate, product, and transition state, molecular dynamic simulation
-
-
-
additional information
?
-
-
the 3'-OH group is important for nucleotide binding, substrate analogues and substrate specificity, overview
-
-
-
additional information
?
-
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
no substrate: deoxycytidine, no substrates: deoxyadenosine, deoxyguanosine, specific for deoxyribonucleosides
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
intact platelets degrade thymidine but are not able to synthesize thymidine from thymine
-
-
-
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
the enzyme confers resistance to apoptosis induced by hypoxia. The enzymatic degradation of thymidine by thymidine phosphorylase is required for the inhibition of hypoxia-induced apoptosis. The enzyme can confer resistance to apoptosis in addition to its angiogenic activity. The enzyme must play some role in the development or malignancy of tumors. Involved in invasion and metastasis of some solid tumors
-
-
?
thymidine + phosphate
thymine + 2-deoxy-D-ribose 1-phosphate
show the reaction diagram
-
the enzyme plays a crucial role in intratumoral angiogenesis, which occurs in the early phase of ovarian cancer, or influences angiogenesis indirectly
-
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
-
-
r
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
-
-
2-deoxy-alpha-D-ribose 1-phosphate strongly promoted neovascularization
-
?
thymidine + phosphate
thymine + 2-deoxy-alpha-D-ribose 1-phosphate
show the reaction diagram
Mus musculus C57Bl6/J
-
-
-
-
r
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
-
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
-
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
enzyme is enantioselective, acts only on the naturally occurring D-thymidine and some D-thymidine analogs, but not on their L-counterparts
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
in Escherichia coli and Salmonella typhimurium thymidine phosphorylase plays an important role in metabolism of thymine auxotrophs and is necessary for the conversion of exogenous thymine to thymidine
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
enzyme also catalyzes the nucleoside deoxyribosyltransferase reaction with pyrimidine deoxyribonucleosides, ec2.4.2.6
-
-
-
thymine + 2-deoxy-D-ribose 1-phosphate
thymidine + phosphate
show the reaction diagram
-
degradation of uridine in tumor specimen
-
-
-
5-fluorouracil + 2-deoxy-alpha-D-ribose 1-phosphate
5-fluoro-2'-deoxyuridine + phosphate
show the reaction diagram
-
the enzyme converts 5-fluorouracil to 5-fluoro-2'-deoxyuridine, activating the prodrug, overview. This action can only take place if there is enough co-substrate. 5-Fluorouracil prodrugs and metabolism, detailed overview
5-fluoro-2'-deoxyuridine is further converted by thymidine kinase to 5-fluoro-2'-deoxyuridine 5'-monophosphate
-
?
additional information
?
-
-
role in thymidine metabolism, homeostasis, development and regeneration of central nervous system and formation of blood/brain barrier
-
-
-
additional information
?
-
-
formation of blood/brain barrier and repair following brain injury
-
-
-
additional information
?
-
-
identical to platelet-derived endothelial cell growth factor
-
-
-
additional information
?
-
-
mitogenic effect, promotes endothelial cell proliferation
-
-
-
additional information
?
-
-
angiogenic activity
-
-
-
additional information
?
-
-
expression of PD-ECGF/TP may play an important role in the progression of solid tumors
-
-
-
additional information
?
-
-
important role in nucleoside metabolism, implicated in angiogenesis and apoptosis
-
-
-
additional information
?
-
-
thymidine phosphorylase and uridine phosphorylase contribute in the conversion of 5'-deoxy-5-fluorouridine into 5-fluorouracil and the conversion of 5-fluorouracil into its active metabolites in peripheral blood mononuclear cell, but thymidine phosphorylase seems to be the most important enzyme for these reactions in PBMC
-
-
-
additional information
?
-
-
the enzyme stimulates formation of focal adhesions and the phosphorylation of Tyr397 of focal adhesion kinase, and it induces the expression and/or secretion of other angiogenic factors, overview. Thymidine phosphorylase promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis, detailed overview. As gliostatin from fibroma cells, the enzyme inhibits the growth of both astrocytes and glial tumor cells
-
-
-
additional information
?
-
-
thymidine phosphorylase is identical with platelet-derived endothelial cell growth factor, PD-ECGF, which promotes angiogenesis. The mechanism of endometrial angiogenesis involves thymidine phosphorylase and stimulation by ovarian steroids of production of angiogenic regulators by endometrial epithelium and stroma which then act on the endothelium
-
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2,4,5-trioxo-3-phenethyl-imidazolidin-1-yl)ethanoic acid
-
-
(4xi)-2',3'-O-[(1R)-2-carboxyethylidene]-5-methylcytidine
-
-
(4xi)-5-methyl-2',3'-O-[(1R)-2-phosphonoethylidene]cytidine
-
-
(R)-(1-fluoro-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propan-2-yloxy)methylphosphonic phosphoric anhydride
-
strong inhibitory effect
(R)-1-[2-(phosphonomethoxy)propyl]thymine
-
-
(R)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
-
(R)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
93% inhibition at 0.01 mM
(R)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
at 0.01 mM, 82% inhibition of V79 cell-expressed thymidine phosphorylase, 56% inhibition of thymidine phosphorylase from placenta
(R)-1-[3-fluoro-2-(phosphonomethoxy)propyl]thymine
-
efficient inhibitor
(R)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
-
(R)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
98% inhibition at 0.01 mM
(R)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
at 0.01 mM, 84% inhibition of V79 cell-expressed thymidine phosphorylase, 84% inhibition of thymidine phosphorylase from placenta
(S)-(1-fluoro-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)propan-2-yloxy)methylphosphonic phosphoric anhydride
-
strong inhibitory effect
(S)-1-[2-(phosphonomethoxy)propyl]thymine
-
-
(S)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
-
(S)-1-[3-fluoro-2-(phosphonomethoxy)propyl]thymine
-
efficient inhibitor
(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
-
([(1R)-2-fluoro-1-[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
-
([(1R)-2-fluoro-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; 98% inhibition at 0.01 mM
([(1R)-2-fluoro-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; at 0.01 mM, complete inhibition of V79 cell-expressed thymidine phosphorylase
([(1R)-2-fluoro-1-[(5-methyl-2,6-dioxotetrahydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
low inhibitory effect
([(1R)-2-hydroxy-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; complete inhibition at 0.01 mM
([(1R)-2-hydroxy-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; at 0.01 mM, 91% inhibition of V79 cell-expressed thymidine phosphorylase, 79% inhibition of thymidine phosphorylase from placenta
([(1S)-2-fluoro-1-[(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
-
([(1S)-2-fluoro-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; 93% inhibition at 0.01 mM
([(1S)-2-fluoro-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; at 0.01 mM, complete inhibition of V79 cell-expressed thymidine phosphorylase
([(1S)-2-fluoro-1-[(5-methyl-2,6-dioxotetrahydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
low inhibitory effect
([(1S)-2-hydroxy-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; 94% inhibition at 0.01 mM
([(1S)-2-hydroxy-1-[(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
; at 0.01 mM, complete of V79 cell-expressed thymidine phosphorylase, 95% inhibition of thymidine phosphorylase from placenta
([2,2,2-trifluoro-1-[(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl]ethoxy]methyl)phosphonic acid
-
-
([[(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3-yl]oxy]methyl)phosphonic acid
-
-
1-(2''-deoxy-beta-D-threo-pentafuranosyl)thymine
-
-
1-(2'-deoxy-beta-D-threo-pentafuranosyl)thymine
-
;
1-(2-hydroxyethoxymethyl)thymine
-
-
1-(8-phosphonooctyl)-6-amino-5-bromouracil
-
competitive
1-(8-phosphonooctyl)-7-deazaxanthine
-
competitive
1-benzyl-imidazolidine-2,4,5-trione
-
-
1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]thymine
-
-
1-[2-(phosphono-methoxy)ethyl]thymine
-
-
1-[2-(phosphonomethoxy)ethyl]thymine
-
complete inhibition at 0.01 mM
1-[2-(phosphonomethoxy)ethyl]thymine
-
at 0.01 mM, complete inhibition of V79 cell-expressed thymidine phosphorylase, 85% inhibition of thymidine phosphorylase from placenta
1-[2-deoxy-3,5-O-[phenyl(phosphono)methylidene]-b-L-erythro-pentofuranosyl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
53% inhibition at 0.01 mM; 96% inhibition at 0.01 mM
1-[3,5-O-(2-bromo-1-phosphonoethylidene)-2-deoxy-b-L-erythro-pentofuranosyl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
74% inhibition at 0.01 mM; 80% inhibition at 0.01 mM
2',3'-Dideoxy-5-ethyluridine
-
9% inhibition at 10 mM
2,2'-O-anhydrouridine
-
-
2-deoxy-D-ribose
-
product inhibition
2-deoxy-D-ribose
-
product inhibition
2-deoxy-D-ribose
-
competitive
2-deoxy-L-ribose
-
-
2-mercapto-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-one
-
25% inhibition at 0.045 mM
2-mercapto-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-one
-
-
3'-amino-3'-deoxythymidine
-
;
3'-Azido-2',3'-dideoxy-5-ethyluridine
-
16% inhibition at 10 mM
3'-Azido-2',3'-dideoxy-5-methyluridine
-
6% inhibition at 10 mM
3'-Bromo-2',3'-dideoxy-5-ethyluridine
-
9% inhibition at 5 mM
3'-Chloro-2',3'-dideoxy-5-ethyluridine
-
26% inhibition at 10 mM
3'-Chloro-2',3'-dideoxy-5-methyluridine
-
18% inhibition at 10 mM
3'-Deoxythymidine
-
;
3-(2,4,5-trioxo-3-phenethyl-imidazolidin-1-yl)-propionamide
-
-
3-([(1-benzyl-2-hydroxyethyl)imino]methyl)-4Hchromen-4-one
-
-
3-([(2, 4-dichlorophenyl)imino]methyl)-4H-chromen-4-one
-
-
3-([(2-([-(4-oxo-4H-chromen-3-yl)methylidene]amino)ethyl)imino] methyl)-4H-chromen-4-one
-
-
3-([(2-benzoyl-4-chlorophenyl)imino]methyl)-4Hchromen-4-one
-
-
3-([(2-methyl-6-nitrophenyl)imino]methyl)-4Hchromen-4-one
-
-
3-([(3-hydroxy-2-pyridinyl)imino]methyl)-4H-chromen-4-one
-
-
3-([(3-methoxy-4-methylphenyl)imino]methyl)-4Hchromen-4-one
-
-
3-([(3-methylphenyl)imino]methyl)-4H-chromen-4-one
-
-
3-benzoyl-5-chloropyrimidine-2,4(1H,3H)-dione
-
-
3-[3-(3-chlorobenzyl)-2,4,5-trioxo-imidazolidin-1-yl]-propionamide
-
-
4,6-dihydroxy-5-nitropyrimidine
-
0.1 mM, competitive
5'-azido-5'-deoxythymidine
-
-
5'-bromo-5'-deoxythymidine
-
;
5'-chloro-5'-deoxythymidine
-
-
5'-iodo-5'-deoxythymidine
-
;
5'-O-trityl-inosine
-
i.e. KIN59, IC50: 0.044 mM, noncompetitively inhibits, when thymidine or phosphate is the variable substrate. Suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action
5'-O-trityl-inosine
-
i.e. KIN59, IC50: 0.067 mM, noncompetitively inhibits, when thymidine or phosphate is the variable substrate. Suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action
5'-O-trityl-inosine
-
IC50: 0.044 mM, reversible, noncompetitive inhibition with respect to thymidine and phosphate
5'-O-trityl-inosine
-
IC50: 0.067 mM, reversible, noncmpetitive
5'-O-tritylinosine
-
-
5'-O-tritylinosine
-
i.e. KIN59, noncompetitive. Inhibitor docking and conformational changes, molecular modeling using the crystal structure of the enzyme, molecular dynamics simulations, binding site and mode, overview
5'-O-tritylinosine
-
i.e. KIN59, a small-molecule inhibitor. KIN59 not only prevents the formation of new blood vessels but also promotes the degradation of small pre-existing immature blood vessels, not due to unspecific cell toxicity
5-amino-6-chlorouracil
-
-
5-benzyl-6-chloropyrimidine-2,4(1H,3H)-dione
-
-
5-benzylacyclouridine
-
-
5-bromo-2-deoxyuridine
-
100% inhibition at 10 mM
5-bromo-6-(2-imino-pyrrolidin-1-yl)methyl-uracil
-
tightbinding stoichiometric inhibitor of recombinant Escherichia coli thymidine phosphorylase, can be used as active-site titrants for it using either thymidine or 5-nitro-2'-deoxyuridine as substrate
5-bromo-6-(3'-methylimidazol-1-yl)uracil
-
IC50: 0.038 mM
5-bromo-6-amino-uracil
-
enzyme inhibition results in a significant increase in basal and oxidative stress-induced apoptosis, the effect is abrogated by supplementation with 2-deoxy-D-ribose-1-phosphate
5-bromo-6-aminouracil
-
-
5-bromo-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0244 mM
5-bromo-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.16 mM
5-bromo-6-[(3-methylimidazol-1-yl)methyl]uracil
-
IC50: 0.017 mM
5-bromo-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0066 mM
5-bromo-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.181 mM
5-Bromouracil
-
0.1 mM, competitive
5-butyl-6-chloropyrimidine-2,4(1H,3H)-dione
-
-
5-chloro-6-(2-imino-pyrrolidin-1-yl)methyluracil
-
tightbinding stoichiometric inhibitor of recombinant Escherichia coli thymidine phosphorylase, can be used as active-site titrants for it using either thymidine or 5-nitro-2'-deoxyuridine as substrate
5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride
-
-
5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4-(1H,3H)-pyrimidine
-
-
5-chloro-6-(3'-methylimidazol-1-yl)uracil
-
IC50: 0.035 mM
5-chloro-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0217 mM
5-chloro-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.115 mM
5-chloro-6-[(3-methylimidazol-1-yl)methyl]uracil
-
IC50: 0.018 mM
5-chloro-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.007 mM
5-chloro-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.2 mM
5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil hydrochloride
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracil
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracil hydrochloride
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracil hydrochloride
-
-
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracilhydrochloride
-
-
5-chloro-6-[1-(imminopyrrolidinyl)methyl]uracil hydrochloride
-
i.e. TPI, competitive
5-chloro-6-[1-(imminopyrrolidinyl)methyl]uracil hydrochloride
-
-
5-ethyl-1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]uracil
-
-
5-ethyl-1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]uracil
-
-
5-ethyl-1-[(S)-3-fluoro-2-(phosphonomethoxy)propyl]uracil
-
-
5-fluoro-1-(tetrahydrofur-2-yl)uracil
-
-
5-fluoro-6-(1H-imidazol-1-ylmethyl)pyrimidine-2,4(1H,3H)-dione
-
-
5-fluoro-6-([[2-hydroxy-1-(hydroxymethyl)ethyl]amino]methyl)pyrimidine-2,4(1H,3H)-dione
-
-
5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil
-
i.e. AIFU, synthesis, overview, uncompetitive with respect to phosphate, acts as transition state analogs, mimicking the anionic thymine leaving group anchored by their protonated side chains to the enzyme-bound phosphate by electrostatic and H-bonding interactions, modeling of ligand binding at the active site, overview
5-fluoro-6-[(4H-1,2,4-triazol-4-ylamino)methyl]pyrimidine-2,4(1H,3H)-dione
-
-
5-fluorodeoxyuridine
-
80% inhibition at 10 mM
5-fluorouracil
-
0.1 mM, competitive
5-Hydroxymethyluracil
-
35% inactivation at 2 mM
5-Iodouracil
-
His116 directly interacts with the inhibitor via its NE2 group, enzyme binding structure, overview
5-methyluridine
-
-
5-Nitrouracil
-
0.1 mM, competitive
5-phenyl-6-pyrrolidin-1-ylpyrimidine-2,4(1H,3H)-dione
-
-
5-[(1E)-but-1-en-1-yl]-6-chloropyrimidine-2,4(1H,3H)-dione
-
-
6-(1H-imidazol-1-ylmethyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-(2-amino-imidazol-1-yl)methyl-5-bromouracil
-
tightbinding stoichiometric inhibitor of recombinant Escherichia coli thymidine phosphorylase, can be used as active-site titrants for it using either thymidine or 5-nitro-2'-deoxyuridine as substrate
6-(2-amino-imidazol-1-yl)methyl-5-chlorouracil
-
tightbinding stoichiometric inhibitor of recombinant Escherichia coli thymidine phosphorylase, can be used as active-site titrants for it using either thymidine or 5-nitro-2'-deoxyuridine as substrate
6-(2-aminoethyl)amine-5-chlorouracil
-
AEAC
6-(3-methylimidazol-1-yl)uracil
-
IC50: 0.110 mM
6-(4-phenlybutylamino)uracil
-
PBAU, 50% inhibition at 0.03 mM
6-(4H-1,2,4-triazol-4-ylmethyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-([[2-hydroxy-1-(hydroxymethyl)ethyl]amino]methyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-amino-5-bromouracil
-
-
6-amino-5-bromouracil
-
-
6-amino-5-bromouracil
-
-
6-amino-5-chlorouracil
-
inhibits angiogenic activity, competitive
6-amino-5-chlorouracil
-
-
6-aminothymine
-
-
6-aminouracil
-
0.1 mM, competitive
6-benzyl-2-thiouracil
-
0.1 mM, mixed inhibition
6-bromo-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(1-methylethenyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(2-naphthyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(2-thienyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(3,5-dimethylphenyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-(4-fluorophenyl)pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-cyclohex-1-en-1-ylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-cyclopent-1-en-1-yluracil
-
-
6-chloro-5-ethylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-heptylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-hexylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-pentylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-propylpyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-pyridin-3-ylpyrimidine-2,4(1H,3H)-dione hydrochloride
-
-
6-chloro-5-[(1E)-1-ethylprop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-[(1E)-pent-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
-
6-chloro-5-[(1E)-prop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
-
6-fluoro-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-methyl-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-Methyluracil
-
competitive, 86% inhibition at 10 mM and 36% inhibition at 1 mM
6-[(2'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.0000187 mM
6-[(2'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.000019 mM
6-[(2'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: below 0.0000206 mM
6-[(2'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: below 0.000049 mM
6-[(2'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.00056 mM
6-[(2'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.0001 mM
6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0024 mM
6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.2577 mM
6-[(2-aminoethyl)amino]-5-phenylpyrimidine-2,4(1H,3H)-dione
-
-
6-[(3-methylimidazol-1-yl)methyl]thymine
-
IC50: 0.06 mM
6-[(3-methylimidazol-1-yl)methyl]uracil
-
IC50: 0.042 mM
6-[(4'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.00065 mM
6-[(4'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.041 mM
6-[(4'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: 0.00073 mM
6-[(4'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: 0.026 mM
6-[(4'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.1014 mM
6-[(4'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.143 mM
6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0138 mM
6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.5 mM
7-deazaxanthine
-
competitive, 50% inhibition at 0.04 mM
7-deazaxanthine
-
-
7-deazaxanthine
-
-
9-[8-phosphonooctyl]-7-deazaxanthine
-
-
allyloxymethylthymine
-
0.1 mM, uncompetitive
Arabinofuranosyl-5-ethyluracil
-
10% inhibition at 10 mM
aurothioglucose
-
the expression of tyhmidine phosphorylase mRNA is significantly decreased by stimulation with aurothioglucose
Bromouracil
-
100% inactivation at 1 mM
deoxyadenosine
-
20% inactivation at 1 mM
deoxyribose-1-phosphate
-
-
dexamethasone
-
the expression of tyhmidine phosphorylase mRNA is significantly decreased by stimulation with dexamethasone
diethyl ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)(difluoro)methyl)phosphonate
-
-
diethyl ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
-
diethyl ((2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
-
diethyl (2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]benzyl)phosphonate
-
-
diethyl ([2-(hydroxymethyl)cyclopent-1-en-1-yl]methyl)phosphonate
-
-
diethyl [(Z)-4-(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)but-2-en-1-yl]phosphonate
-
-
diethyl [(Z)-4-hydroxybut-2-en-1-yl]phosphonate
-
-
diethyl [2-(hydroxymethyl)benzyl]phosphonate
-
-
disodium ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)(difluoro)methyl)phosphonate
-
-
disodium ((2-[(3,4-dihydro-5-methyl-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
-
disodium ((2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]cyclopent-1-en-1-yl)methyl)phosphonate
-
-
disodium (2-[(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)methyl]benzyl)phosphonate
-
-
disodium [(Z)-4-(5-chloro-3,4-dihydro-2,4-dioxopyrimidin-1(2H)-yl)but-2-en-1-yl]phosphonate
-
-
ftorafur
-
; ftorafur is also called tegafur
hydrogen [[(1R,2S,4S)-2-(hydroxymethyl)-4-(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)pyrrolidinium-1-yl]methyl]phosphonate
-
-
KIN56
-
IC50: 0.232 mM
KIN56
-
IC50: 0.351 mM
N'-[-(4-oxo-4H-chromen-3-yl)methylidene]propanohydrazide
-
-
NSC 122612
-
0.12 mM, 27% inhibition
NSC 19791
-
0.89 mM, 14% inhibition
-
NSC 23145
-
0.105 mM, 23% inhibition
NSC 298251
-
0.1 mM, 30% inhibition
NSC 3056
-
0.089 mM, 24% inhibition
NSC 309091
-
0.13 mM, 21% inhibition
NSC 357688
-
0.09 mM, 28% inhibition
NSC 43275
-
0.106 mM, 16% inhibition
NSC 6487
-
0.089 mM, 6% inhibition
NSC 65043
-
0.093 mM, 84% inhibition, linear competitive
NSC 65043
-
IC50: 0.077 mM
NSC 659977
-
0.134 mM, 60% inhibition
NSC 81031
-
0.93 mM, 15% inhibition
p-chloromercuribenzoate
-
above 0.01 mM
prostaglandin E2
-
-
ribose 1-phosphate
-
competitive
ribose 1-phosphate
-
20% inactivation at 1.5 mM
SO42-
-
inhibition reversed by phosphate
thymidine phosphorylase inhibitor
-
-
-
thymine
-
product inhibition; substrate inhibition
Uracil
-
inhibits activity in turmor tissue, but not in normal tissue
Urea
-
inhibition at high concentration, 4 M, stimulation at low concentration
uridine
-
competitive 27% inactivation at 1 mM
uridine
-
-
uridine
-
-
xanthine
-
13% inhibition at 0.158 mM
xanthine
-
-
[(2S,3aR,4R,6R,6aR)-4-(5-chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-6-(hydroxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
[(2S,4R,5S)-5-(2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxy-1,3-oxazolidin-2-yl]phosphonic acid
-
-
[(3aR,4R,6R,6aR)-4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-6-(hydroxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
[(3aR,4R,6R,6aR)-4-(hydroxymethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
[2-[(3S)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]-2-oxoethyl]phosphonic acid
-
41% inhibition at 0.01 mM
[5-[2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy]pentyl]phosphonic acid
-
86% inhibition at 0.01 mM
[6-[2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy]hexyl]phosphonic acid
-
79% inhibition at 0.01 mM
[8-(2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-1-yl)octyl]phosphonic acid
-
-
[8-(2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-1-yl)octyl]phosphonic acid
-
no antitumor activity found with CCRF-CEM T-lymphoblastoid cells, human promyelocytic leukemia HL-60 cells, human cervix carcinoma HeLa S3 cells
[8-(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidin-1-yl)octyl]phosphonic acid
-
-
[8-(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidin-1-yl)octyl]phosphonic acid
-
no antitumor activity found with CCRF-CEM T-lymphoblastoid cells, human promyelocytic leukemia HL-60 cells, human cervix carcinoma HeLa S3 cells
[[(1R)-2-(5-ethyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1-(fluoromethyl)ethoxy]methyl]phosphonic acid
-
-
[[(2R,3aR,6aR)-6-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-4-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
[[(2R,4R)-2-(hydroxymethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]methyl]phosphonic acid
-
83% inhibition at 0.01 mM
[[(2R,4S)-2-(hydroxymethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
98% inhibition at 0.01 mM
[[(2R,4S)-2-(hydroxymethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]methyl]phosphonic acid
-
complete inhibition at 0.01 mM
[[(2S,3aR,6aR)-6-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-4-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
[[(2S,3aR,6aS)-4-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-6-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
[[(2S,4S)-2-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonothioyl]phosphonic acid
-
complete inhibition at 0.01 mM
[[(2S,4S)-2-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
complete inhibition at 0.01 mM
[[(3R,4R)-3-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
96% inhibition at 0.01 mM
[[(3R,4R)-3-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]methyl]phosphonic acid
-
99% inhibition at 0.01 mM
[[(3S)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonothioyl]phosphonic acid
-
91% inhibition at 0.01 mM
[[(3S)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
97% inhibition at 0.01 mM
[[(3S)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]methyl]phosphonic acid
-
71% inhibition at 0.01 mM
[[(3S,4R)-3-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
-
[[2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy]methyl]phosphonic acid
-
-
[[2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1-(prop-2-en-1-yloxy)ethoxy]methyl]phosphonic acid
-
90% inhibition at 0.01 mM
[[2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1-phenoxyethoxy]methyl]phosphonic acid
-
99% inhibition at 0.01 mM
[[2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy](phenyl)methyl]phosphonic acid
-
91% inhibition at 0.01 mM
[[2-(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)ethoxy]methyl]phosphonic acid
-
; complete inhibition at 0.01 mM
[[2-(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)ethoxy]methyl]phosphonic acid
-
; at 0.01 mM, complete inhibition of V79 cell-expressed thymidine phosphorylase, 82% inhibition of thymidine phosphorylase from placenta
methyluridine
-
-
additional information
-
photoinactivation in presence of thymine, thymidine and some halogenated analogs
-
additional information
-
a specific thymidine phosphorylase inhibitor TPI completely inhibits
-
additional information
-
-
-
additional information
-
iodination reduces activity, 63% inactivation after 5 min and complete inactivation after 20 min
-
additional information
-
5- and 6-substituted uracil analogs
-
additional information
-
no inhibition by 5'-deoxy-5-fluorouridine
-
additional information
-
thymidine phosphorylase and its degradation product 2-deoxy-D-ribose suppress hypoxia-induced apoptosis, the upregulation of hypoxia-inducible factor 1alpha and the proapoptotic factor, BNIP3, and caspase 3 activation induced by hypoxia
-
additional information
-
thymidine phosphorylase promoter methylation is a mechanism for down-regulation of enzyme expression in cancer cells
-
additional information
-
not inhibited by 5-chloro-6-methyl-3H-pyrimidin-4-one, 5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]-3H-pyrimidin-4-one, 6H-imidazo[1,2-c]pyrimidin-5-one, 7H-pyrrolo[2,3-d]pyrimidin-2(1H)-one, and 7H-pyrrolo[2,3-d]pyrimidine
-
additional information
-
not inhibited by 1-[(4S,5R)-4-hydroxyisoxazolidin-5-yl]-5-methylpyrimidine-2,4(1H,3H)-dione
-
additional information
-
capecitabine does not affect enzyme activity and expression
-
additional information
-
Schiff bases of 3-formylchromone as thymidine phosphorylase inhibitors, no inhibition by 3-formylchromone and 3-methyl-7-hydroxychromone, and by derivatives 3-[(4-pyridinylimino) methyl]-4H-chromen-4-one, 3-[(3-pyridinylimino) methyl]-4H-chromen-4-one, 3-([(3-methoxyphenyl)imino]methyl)-4H-chromen-4-one, 3-([(2-methoxy-4-nitrophenyl) imino] methyl)-4Hchromen-4-one, 2-([-(4-oxo-4H-chromen-3-yl) methylidene]amino)benzoic acid, 3-([(4-methylphenyl)imino]methyl)-4H-chromen-4-one, 3-([(2,6-dimethylphenyl)imino]methyl)-4H-chromen-4-one, and 3-[bis(tert-butylamino)methyl]-4H-chromen-4-one, overview
-
additional information
-
synthesis of 5-alkyl, 5-aryl, or 5-fluoro derivatives of 1-[2-(phosphonomethoxy)-ethyl]thymine inhibitors that mimic the interatomic distance between the incoming phosphate and leaving pyrimidine groups at the transition state for the putative SN2 mechanism of thymidine phosphorylase, structures, the inhibitors are not effective compared to (phosphonomethoxy)-alkyl-pyrimidine inhibitors, overview. Switching the N1-linked side chains found in 1-[2-(phosphonomethoxy)-ethyl]thymine, 1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]thymine and 1-[(R)-3-fluoro-2-(phosphonomethoxy)propyl]thymine to the N3-position of the nucleobases resulted in significant loss of activity. Replacement of the iminopyrrolidine ring found in 5-ethyl-1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]uracil with a 3-methylimidazol-3-ium ring leads to a series of less active 5-halo-6-[(3-methylimidazol-3-ium-1-yl)methyl]-uracil chlorides. On the other hand, replacement with a 2-aminoimidazole ring, leads to a number of 6-[(2-aminoimidazol-1-yl)methyl]-5-chloro-(and 5-bromo)uracil hydrochlorides with similar inhibitory strength compared to 5-ethyl-1-[(R)-3-hydroxy-2-(phosphonomethoxy)propyl]uracil, computer-modeling simulations, overview
-
additional information
-
enzyme inhibitors can abrogate the tumorigenic and metastatic properties of the enzyme, e.g. 2-deoxy-L-ribose, which does not inhibit the enzyme but affects its biological functions
-
additional information
-
inhibitory nucleotide derivatives, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cyclophosphamide
-
thymidine phosphorylase expression is upregulated after treatment with 600 mg/m2 cyclophosphamide
cyclophosphamide
-
induces thymidine phosphorylase expression
docetaxel
-
induces thymidine phosphorylase expression
Doxorubicin
-
thymidine phosphorylase expression is upregulated after treatment with 60 mg/m2 doxorubicin
epirubicin
-
thymidine phosphorylase expression is upregulated after treatment with 75 mg/m2 epirubicin
interferon alpha
-
causes a rapid and transient increase of thymidine phosphorylase expression
-
interferon alpha
-
-
-
interferon alpha2b
-
induces thymidine phosphorylase mRNA and protein expression in a dose-dependent manner
-
interferon beta
-
causes a rapid and transient increase of thymidine phosphorylase expression
-
interferon gamma
-
causes a rapid and transient increase of thymidine phosphorylase expression
-
Interleukin-1beta
-
the expression of tyhmidine phosphorylase mRNA is significantly increased by stimulation with interleukin-1beta
-
paclitaxel
-
the expression of thymidine phosphorylase mRNA is up-regulated by the administration of paclitaxel (20 mg/kg)
paclitaxel
Q99N42
the expression of thymidine phosphorylase mRNA is up-regulated by the administration of paclitaxel (20 mg/kg)
paclitaxel
-
induces thymidine phosphorylase expression
Tumor necrosis factor alpha
-
causes a rapid and transient increase of thymidine phosphorylase expression
-
Tumor necrosis factor alpha
-
-
-
Urea
-
stimulates at low concentration, inhibits at high concentration, 4 M
mitomycin C
-
induces thymidine phosphorylase expression
additional information
-
thymidine phosphorylase demonstrates differential expression depending on age, there is no remarkable difference in the mRNA and protein expression of thymidine phosphorylase due to the response in chemotherapy with TS-1
-
additional information
-
the enzymatic activity of thymidine phosphorylase is required for the activation of 5-fluorouracil prodrugs, the enzyme induces the expression of several matrix metalloproteinases, increases the levels of hypoxia-inducible factor 1alpha during in vitro hypoxia
-
additional information
-
no activation of protein expression by paclitaxel, therefore no increased haematotoxicity due to thymidine phosphorylase upregulation is expected from the combination of taxanes and capecitabine
-
additional information
-
50.4 Gy radiation in combination with capecitabine leads to elevated thymidine phosphorylase activity
-
additional information
-
thymidine phosphorylase expression is not up-regulated after docetaxel treatment
-
additional information
-
heterogeneous ribonucleoprotein K regulates thymidine phosphorylase mRNA stability
-
additional information
-
preoperative radiotherapy (cumulative dose of 45 Gy) and concomitant capecitabine (825 mg/m2) treatment induce 2.3fold increase of thymidine phosphorylase mRNA levels
-
additional information
-
gliostatin has a role in regulating vascular endothelial growth factor
-
additional information
-
capecitabine does not affect enzyme activity and expression
-
additional information
-
the enzyme is activated in several diseases, detailed overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.35
1-(2',6'-dideoxy-alpha-L-lyxo-hexafuranosyl)thymine
-
25C, pH 6.5
0.35
1-(2',6'-dideoxy-alpha-L-lyxohexafuranosyl)thymine
-
in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.33
1-(2',6'-dideoxy-beta-D-ribo-hexafuranosyl)thymine
-
25C, pH 6.5
0.3
1-(2',6'-dideoxy-beta-D-ribohexafuranosyl)thymine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.33
1-(2',6'-dideoxy-beta-D-ribohexafuranosyl)thymine
-
in 50 mM potassium phosphate buffer (pH 6.5), at 25C
13.3
1-(Tetrahydro-2-furanyl)-5-fluorouracil
-
-
0.32
2'-deoxyuridine
-
-
0.4
3'-amino-3'-deoxythymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.35
3'-deoxy-2',3'-didehydrothymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
10
3'-Deoxythymidine
-
in 50 mM phosphate buffer, pH 6.8
0.25
4-thiothymidine
-
pH 7.5, 25C
0.28
4-thiothymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.4
5'-amino-5'-deoxythymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.3
5'-chloro-5'-deoxythymidine
-
25C, pH 6.5
1.72
5'-deoxy-5-fluorouridine
-
-
0.4
5'-Deoxythymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
32
5'-Deoxythymidine
-
in 50 mM phosphate buffer, pH 6.8
0.16
5-nitro-2'-deoxyuridine
-
pH 7.4, 25C
0.16
5-nitro-2'-deoxyuridine
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25C
0.23
5-nitro-2'-deoxyuridine
-
pH 7.4, 25C
0.23
5-nitro-2'-deoxyuridine
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25C
0.00064
phosphate
-
37C, pH 7.4
0.019
phosphate
-
-
0.1
phosphate
-
-
0.89
phosphate
-
-
0.00166
thymidine
-
-
0.043
thymidine
-
37C, pH 7.4
0.11
thymidine
-
-
0.168
thymidine
-
-
0.24
thymidine
-
pH 7.4, 25C
0.3
thymidine
-
pH 7.5, 25C
0.3
thymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.35
thymidine
-
ph 5.5, 37C, recombinant wild-type enzyme
0.38
thymidine
-
-
0.42
thymidine
-
ph 5.5, 37C, recombinant mutant K115A
0.65
thymidine
-
normal tissue
0.74
thymidine
-
ph 5.5, 37C, recombinant mutant I214A
0.945
thymidine
-
-
2.1
thymidine
-
ph 5.5, 37C, recombinant mutant Y199F
2.5
thymidine
-
in 50 mM phosphate buffer, pH 6.8
3.14
thymidine
-
ph 5.5, 37C, recombinant mutant Y199L
9.3
thymidine
-
tumor tissue
0.0832
thymine
-
pH 6.7
0.141
thymine
-
-
0.414
thymine
-
pH 7.6, wild-type enzyme
9.828
thymine
-
pH 7.6, mutant D203A
47.6
uridine
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
steady-state kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.45
1-(2',6'-dideoxy-alpha-L-lyxo-hexafuranosyl)thymine
-
25C, pH 6.5
0.45
1-(2',6'-dideoxy-alpha-L-lyxohexafuranosyl)thymine
-
in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.1
1-(2',6'-dideoxy-beta-D-ribo-hexafuranosyl)thymine
-
25C, pH 6.5
0.1
1-(2',6'-dideoxy-beta-D-ribohexafuranosyl)thymine
-
in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.6
1-(2',6'-dideoxy-beta-D-ribohexafuranosyl)thymine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
35
2'-deoxyuridine
-
-
1.1
3'-amino-3'-deoxythymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.4
3'-deoxy-2',3'-didehydrothymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
63
4-thiothymidine
-
pH 7.5, 25C
63
4-thiothymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
0.58
5'-amino-5'-deoxythymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
1.7
5'-chloro-5'-deoxythymidine
-
-
260
5'-Deoxythymidine
-
; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
2.88
5-nitro-2'-deoxyuridine
-
pH 7.4, 25C
20
5-nitro-2'-deoxyuridine
-
pH 7.4, 25C
20
5-nitro-2'-deoxyuridine
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25C
0.157
thymidine
-
-
3.5
thymidine
-
ph 5.5, 37C, recombinant mutant Y199F
4.4
thymidine
-
ph 5.5, 37C, recombinant mutant Y199L
5.2
thymidine
-
ph 5.5, 37C, recombinant mutant I214A
6.8
thymidine
-
ph 5.5, 37C, recombinant mutant K115A
8.2
thymidine
-
ph 5.5, 37C, recombinant wild-type enzyme
198
thymidine
-
pH 7.5, 25C
198
thymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer (pH 6.5), at 25C
1770
thymidine
-
pH 7.4, 25C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0435
(4xi)-2',3'-O-[(1R)-2-carboxyethylidene]-5-methylcytidine
-
-
0.000236
(4xi)-5-methyl-2',3'-O-[(1R)-2-phosphonoethylidene]cytidine
-
-
0.0019
(R)-1-[2-(phosphonomethoxy)propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: 2'-deoxythymidine
0.00396
(R)-1-[2-(phosphonomethoxy)propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: phosphate
0.00022
(R)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: 2'-deoxythymidine
0.00034
(R)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: phosphate
0.00255
(R)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
enzyme from liver, pH 6.4, 37C, substrate: 2'-deoxythymidine
0.00344
(R)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
enzyme from liver, pH 6.4, 37C, substrate: phosphate
0.00037
(R)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: 2'-deoxythymidine
0.00078
(R)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: phosphate
0.00232
(R)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
enzyme from liver, pH 6.4, 37C, substrate: 2'-deoxythymidine
0.0027
(R)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
enzyme from liver, pH 6.4, 37C, substrate: phosphate
0.00068
(S)-1-[2-(phosphonomethoxy)propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: 2'-deoxythymidine
0.001
(S)-1-[2-(phosphonomethoxy)propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: phosphate
0.0004
(S)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: 2'-deoxythymidine
0.00064
(S)-1-[3-fluoro-2-(phosphonomethoxy)-propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: phosphate
0.00093
(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: 2'-deoxythymidine
0.0013
(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: phosphate
0.45
1-(2''-deoxy-beta-D-threo-pentafuranosyl)thymine
-
25C, pH 6.5
0.45
1-(2'-deoxy-beta-D-threo-pentafuranosyl)thymine
-
in 50 mM potassium phosphate buffer, pH 6.5, 25C
1.5
1-(2-hydroxyethoxymethyl)thymine
-
pH 7.5, 25C, activity with 4-thiothymidine
0.00146
1-[2-(phosphono-methoxy)ethyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: 2'-deoxythymidine
0.00173
1-[2-(phosphono-methoxy)ethyl]thymine
-
enzyme from SD-lymphoma, pH 6.4, 37C, substrate: phosphate
0.4
2,2'-O-anhydrouridine
-
pH 7.5, 25C, activity with 4-thiothymidine
0.5
2,2'-O-anhydrouridine
-
pH 7.5, 25C, activity with thymidine
0.6
3'-amino-3'-deoxythymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer, pH 6.5, 25C
0.85
3'-Deoxythymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer, pH 6.5, 25C
0.021
4,6-dihydroxy-5-nitropyrimidine
-
tumor tissue
0.211
4,6-dihydroxy-5-nitropyrimidine
-
normal tissue
0.4
5'-bromo-5'-deoxythymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer, pH 6.5, 25C
0.4
5'-iodo-5'-deoxythymidine
-
25C, pH 6.5; in 50 mM potassium phosphate buffer, pH 6.5, 25C
0.039
5'-O-trityl-inosine
-
against thymidine
0.146
5'-O-trityl-inosine
-
against phosphate
0.0002
5-benzyl-6-chloropyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00455
5-benzyl-6-chloropyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.0011
5-Bromouracil
-
tumor tissue
0.006
5-Bromouracil
-
normal tissue
0.00103
5-butyl-6-chloropyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00165
5-butyl-6-chloropyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.017
5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione hydrochloride
-
in 50 mM Tris, 1 mM EDTA, pH 7.4, at 37C
0.0000013
5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4-(1H,3H)-pyrimidine
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.0000021
5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4-(1H,3H)-pyrimidine
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.000002
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil hydrochloride
-
-
0.00002
5-chloro-6-[1-(imminopyrrolidinyl)methyl]uracil hydrochloride
-
-
0.4
5-fluoro-1-(tetrahydrofur-2-yl)uracil
-
pH 7.5, 25C, activity with thymidine
0.45
5-fluoro-1-(tetrahydrofur-2-yl)uracil
-
pH 7.5, 25C, activity with 4-thiothymidine
0.000051
5-fluoro-6-(1H-imidazol-1-ylmethyl)pyrimidine-2,4(1H,3H)-dione
-
-
0.001
5-fluoro-6-([[2-hydroxy-1-(hydroxymethyl)ethyl]amino]methyl)pyrimidine-2,4(1H,3H)-dione
-
-
0.000011
5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil
-
-
0.000017
5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil
-
-
0.00037
5-fluoro-6-[(4H-1,2,4-triazol-4-ylamino)methyl]pyrimidine-2,4(1H,3H)-dione
-
-
0.043
5-fluorouracil
-
tumor tissue
0.0728
5-fluorouracil
-
normal tissue
0.48
5-Iodouracil
-
-
0.017
5-methyluridine
-
pH 6.0, recombinant enzyme
0.0051
5-Nitrouracil
-
tumor tissue
0.0253
5-Nitrouracil
-
normal tissue
0.02
5-phenyl-6-pyrrolidin-1-ylpyrimidine-2,4(1H,3H)-dione
-
Km above 0.02 mM, enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C; Km above 0.02 mM, enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00063
5-[(1E)-but-1-en-1-yl]-6-chloropyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00092
5-[(1E)-but-1-en-1-yl]-6-chloropyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.0047
6-(1H-imidazol-1-ylmethyl)pyrimidine-2,4(1H,3H)-dione
-
-
0.000165
6-(2-aminoethyl)amine-5-chlorouracil
-
-
0.054
6-(4H-1,2,4-triazol-4-ylmethyl)pyrimidine-2,4(1H,3H)-dione
-
-
0.0088
6-([[2-hydroxy-1-(hydroxymethyl)ethyl]amino]methyl)pyrimidine-2,4(1H,3H)-dione
-
-
0.0034
6-amino-5-chlorouracil
-
-
0.088
6-aminouracil
-
tumor tissue
0.13
6-aminouracil
-
normal tissue
0.075
6-benzyl-2-thiouracil
-
tumor tissue
0.137
6-benzyl-2-thiouracil
-
normal tissue
0.00121
6-bromo-5-phenylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C; enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00334
6-chloro-5-(1-methylethenyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.0051
6-chloro-5-(1-methylethenyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00394
6-chloro-5-(2-naphthyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00459
6-chloro-5-(2-naphthyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00028
6-chloro-5-(2-thienyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00054
6-chloro-5-(2-thienyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00127
6-chloro-5-(3,5-dimethylphenyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00174
6-chloro-5-(3,5-dimethylphenyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00071
6-chloro-5-(4-fluorophenyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00097
6-chloro-5-(4-fluorophenyl)pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00042
6-chloro-5-cyclohex-1-en-1-ylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00075
6-chloro-5-cyclohex-1-en-1-ylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.0002
6-chloro-5-cyclopent-1-en-1-yluracil
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00029
6-chloro-5-cyclopent-1-en-1-yluracil
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.02
6-chloro-5-ethylpyrimidine-2,4(1H,3H)-dione
-
Km above 0.02 mM, enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C; Km above 0.02 mM, enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.0016
6-chloro-5-heptylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00465
6-chloro-5-heptylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00106
6-chloro-5-hexylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00179
6-chloro-5-hexylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00309
6-chloro-5-pentylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00367
6-chloro-5-pentylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.0004
6-chloro-5-phenylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00043
6-chloro-5-phenylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00402
6-chloro-5-propylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00581
6-chloro-5-propylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00301
6-chloro-5-pyridin-3-ylpyrimidine-2,4(1H,3H)-dione hydrochloride
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00399
6-chloro-5-pyridin-3-ylpyrimidine-2,4(1H,3H)-dione hydrochloride
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00049
6-chloro-5-[(1E)-1-ethylprop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00091
6-chloro-5-[(1E)-1-ethylprop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00041
6-chloro-5-[(1E)-pent-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00091
6-chloro-5-[(1E)-pent-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00117
6-chloro-5-[(1E)-prop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00121
6-chloro-5-[(1E)-prop-1-en-1-yl]pyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.00047
6-fluoro-5-phenylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.0005
6-fluoro-5-phenylpyrimidine-2,4(1H,3H)-dione
-
enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.02
6-methyl-5-phenylpyrimidine-2,4(1H,3H)-dione
-
Km above 0.02 mM, enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C; Km above 0.02 mM, enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
1.6
6-Methyluracil
-
-
0.02
6-[(2-aminoethyl)amino]-5-phenylpyrimidine-2,4(1H,3H)-dione
-
Km above 0.02 mM, enzyme purified from placenta, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C; Km above 0.02 mM, enzyme purified from V79 cells, in 20 mM Bis-Tris-HCl (pH 6.4), at 37C
0.127
allyloxymethylthymine
-
tumor tissue
0.1286
allyloxymethylthymine
-
normal tissue
0.67
deoxyribose-1-phosphate
-
-
0.45
ftorafur
-
25C, pH 6.5; in 50 mM potassium phosphate buffer, pH 6.5, 25C
0.005
hydrogen [[(1R,2S,4S)-2-(hydroxymethyl)-4-(5-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)pyrrolidinium-1-yl]methyl]phosphonate
-
-
2 - 5
NSC 65043
-
-
12.5
NSC 65043
-
-
0.00002
thymidine phosphorylase inhibitor
-
-
-
0.158
Uracil
-
tumor tissue
0.013
uridine
-
pH 6.0, recombinant enzyme
0.06
uridine
-
in 50 mM potassium phosphate buffer, pH 6.5, 25C
0.00077
[(2S,3aR,4R,6R,6aR)-4-(5-chloro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-6-(hydroxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
0.004
[(2S,4R,5S)-5-(2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxy-1,3-oxazolidin-2-yl]phosphonic acid
-
-
0.005
[(3aR,4R,6R,6aR)-4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-6-(hydroxymethyl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
0.01
[(3aR,4R,6R,6aR)-4-(hydroxymethyl)-6-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuro[3,4-d][1,3]dioxol-2-yl]phosphonic acid
-
-
0.0334
[[(2R,3aR,6aR)-6-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-4-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
0.00105
[[(2S,3aR,6aR)-6-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-4-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
0.00803
[[(2S,3aR,6aS)-4-(4-amino-5-methyl-2-oxopyrimidin-1(2H)-yl)-6-(hydroxymethyl)hexahydrofuro[3,4-b]furan-2-yl]methyl]phosphonic acid
-
-
0.01
[[(3S,4R)-3-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
-
0.12
methyluridine
-
in 50 mM potassium phosphate buffer, pH 6.5, 25C
additional information
additional information
-
inhibition kinetics, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.085
(2,4,5-trioxo-3-phenethyl-imidazolidin-1-yl)ethanoic acid
-
pH 7.4, 25C
0.115
1-benzyl-imidazolidine-2,4,5-trione
-
pH 7.4, 25C
0.04
3-(2,4,5-trioxo-3-phenethyl-imidazolidin-1-yl)-propionamide
-
pH 7.4, 25C
0.473
3-([(1-benzyl-2-hydroxyethyl)imino]methyl)-4Hchromen-4-one
-
pH 7.6
0.04
3-([(2, 4-dichlorophenyl)imino]methyl)-4H-chromen-4-one
-
pH 7.6
0.15
3-([(2-([-(4-oxo-4H-chromen-3-yl)methylidene]amino)ethyl)imino] methyl)-4H-chromen-4-one
-
pH 7.6
0.076
3-([(2-benzoyl-4-chlorophenyl)imino]methyl)-4Hchromen-4-one
-
pH 7.6
0.48
3-([(2-methyl-6-nitrophenyl)imino]methyl)-4Hchromen-4-one
-
pH 7.6
0.34
3-([(3-hydroxy-2-pyridinyl)imino]methyl)-4H-chromen-4-one
-
pH 7.6
0.02
3-([(3-methoxy-4-methylphenyl)imino]methyl)-4Hchromen-4-one
-
pH 7.6
0.067
3-([(3-methylphenyl)imino]methyl)-4H-chromen-4-one
-
pH 7.6
0.066
3-[3-(3-chlorobenzyl)-2,4,5-trioxo-imidazolidin-1-yl]-propionamide
-
pH 7.4, 25C
0.044
5'-O-trityl-inosine
-
i.e. KIN59, IC50: 0.044 mM, noncompetitively inhibits, when thymidine or phosphate is the variable substrate. Suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action
0.044
5'-O-trityl-inosine
-
IC50: 0.044 mM, reversible, noncompetitive inhibition with respect to thymidine and phosphate
0.067
5'-O-trityl-inosine
-
i.e. KIN59, IC50: 0.067 mM, noncompetitively inhibits, when thymidine or phosphate is the variable substrate. Suppresses thymidine phosphorylase-triggered angiogenesis via a noncompetitive mechanism of action
0.067
5'-O-trityl-inosine
-
IC50: 0.067 mM, reversible, noncmpetitive
0.038
5-bromo-6-(3'-methylimidazol-1-yl)uracil
-
IC50: 0.038 mM
0.0244
5-bromo-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0244 mM
0.16
5-bromo-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.16 mM
0.017
5-bromo-6-[(3-methylimidazol-1-yl)methyl]uracil
-
IC50: 0.017 mM
0.0066
5-bromo-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0066 mM
0.181
5-bromo-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.181 mM
0.035
5-chloro-6-(3'-methylimidazol-1-yl)uracil
-
IC50: 0.035 mM
0.0217
5-chloro-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0217 mM
0.115
5-chloro-6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.115 mM
0.018
5-chloro-6-[(3-methylimidazol-1-yl)methyl]uracil
-
IC50: 0.018 mM
0.007
5-chloro-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.007 mM
0.2
5-chloro-6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.2 mM
0.000035
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracil
-
-
0.00002
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracilhydrochloride
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25C
0.000023
5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracilhydrochloride
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25C
0.11
6-(3-methylimidazol-1-yl)uracil
-
IC50: 0.110 mM
0.0016
6-amino-5-bromouracil
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25C
0.0068
6-amino-5-bromouracil
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25C
0.0000187
6-[(2'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.0000187 mM
0.000019
6-[(2'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.000019 mM
0.0000206
6-[(2'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: below 0.0000206 mM
0.000049
6-[(2'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: below 0.000049 mM
0.0001
6-[(2'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.0001 mM
0.00056
6-[(2'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.00056 mM
0.0024
6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0024 mM
0.2577
6-[(2'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.2577 mM
0.06
6-[(3-methylimidazol-1-yl)methyl]thymine
-
IC50: 0.06 mM
0.042
6-[(3-methylimidazol-1-yl)methyl]uracil
-
IC50: 0.042 mM
0.00065
6-[(4'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.00065 mM
0.041
6-[(4'-aminoimidazol-1'-yl)methyl]-5-bromouracil
-
IC50: 0.041 mM
0.00073
6-[(4'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: 0.00073 mM
0.026
6-[(4'-aminoimidazol-1'-yl)methyl]-5-chlorouracil
-
IC50: 0.026 mM
0.1014
6-[(4'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.1014 mM
0.143
6-[(4'-aminoimidazol-1'-yl)methyl]uracil
-
IC50: 0.143 mM
0.0138
6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.0138 mM
0.5
6-[(4'-nitroimidazol-1'-yl)methyl]uracil
-
IC50: 0.5 mM
0.0065
7-deazaxanthine
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25C
0.0393
7-deazaxanthine
-
-
0.045
7-deazaxanthine
-
in 0.1 M potassium phosphate buffer (pH 7.4), at 25C
0.232
KIN56
-
IC50: 0.232 mM
0.351
KIN56
-
IC50: 0.351 mM
0.146
N'-[-(4-oxo-4H-chromen-3-yl)methylidene]propanohydrazide
-
pH 7.6
0.077
NSC 65043
-
IC50: 0.077 mM
0.0017
[8-(2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-1-yl)octyl]phosphonic acid
-
enzyme purified from placenta, pH not specified in the publication, temperature not specified in the publication
0.0068
[8-(2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-1-yl)octyl]phosphonic acid
-
pH not specified in the publication, temperature not specified in the publication
0.027
[8-(2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-1-yl)octyl]phosphonic acid
-
recombinant enzyme, pH not specified in the publication, temperature not specified in the publication
0.0073
[8-(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidin-1-yl)octyl]phosphonic acid
-
recombinant enzyme, pH not specified in the publication, temperature not specified in the publication
0.0114
[8-(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidin-1-yl)octyl]phosphonic acid
-
pH not specified in the publication, temperature not specified in the publication
0.0151
[8-(2,4-dioxo-2,3,4,7-tetrahydro-1H-pyrrolo[2,3-d]pyrimidin-1-yl)octyl]phosphonic acid
-
enzyme purified from placenta, pH not specified in the publication, temperature not specified in the publication
0.000045
[[(2R,4S)-2-(hydroxymethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
pH 6.7
0.00025
[[(2R,4S)-2-(hydroxymethyl)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]methyl]phosphonic acid
-
pH 6.7
0.000015
[[(2S,4S)-2-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonothioyl]phosphonic acid
-
pH 6.7
0.000011
[[(2S,4S)-2-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
pH 6.7
0.00022
[[(3R,4R)-3-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
pH 6.7
0.000045
[[(3R,4R)-3-hydroxy-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]methyl]phosphonic acid
-
pH 6.7
0.00019
[[(3S)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonothioyl]phosphonic acid
-
pH 6.7
0.00035
[[(3S)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)pyrrolidin-1-yl]carbonyl]phosphonic acid
-
pH 6.7
0.0003
[[2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1-(prop-2-en-1-yloxy)ethoxy]methyl]phosphonic acid
-
about, pH 6.7
0.00075
[[2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1-phenoxyethoxy]methyl]phosphonic acid
-
pH 6.7
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00002
-
wild-type mouse muscle
0.000205
-
wild-type mouse heart
0.000243
-
TP-/-UP-/- mouse liver
0.000285
-
wild-type mouse spleen
0.00067
-
wild-type mouse kidney
0.000862
-
wild-type mouse lung
0.00136
-
wild-type mouse brain
0.0014
-
wild-type mouse liver
0.00386
-
in normal uterine cervix tissue
0.00527
-
mean thymidine phosphorylase activity in population
0.00946
-
wild-type mouse small intestine
0.01
-
mitochondrial neurogastrointestinal encephalomyopathy syndrome patient, leukocytes
0.04176
-
in cancerous uterine cervix tissue
0.2 - 0.32
-
leukocytes of heterozygous individuals in enzyme mutation and mitochondrial neurogastrointestinal encephalomyopathy syndrome
0.36 - 0.8
-
wild-type activity in leukocytes
1100
-
-
additional information
-
-
additional information
-
-
additional information
-
no activities in other tissues than liver from TP-/-UP-/- mice
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
-
thymine production, assay at
6
-
assay at
6.5
-
assay at
6.7
-
assay at
7.1
-
assay at
7.4
-
assay at
7.5 - 8
-
rapid decrease of activity above and below this range
7.6
-
assay at
7.8
-
assay at
10
-
assay at, pH 10 is used because 2-deoxy-D-ribose 1-phosphate is heat labile at pH 7.4
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.1 - 6.8
-
-
7.5 - 8
-
rapid decrease of activity above and below this range
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
assay at
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
thymidine phosphorylase mRNA levels are low and statistically not different in whole basal cell carcinoma cells and normal skin and are strongly downregulated in laser capture microdissected-basal cell carcinoma cells as compared with laser capture microdissected-normal epidermis
Manually annotated by BRENDA team
-
higher PyNpase levels in normal tissue adjacent to tumor, AN, than in normal tissue, N
Manually annotated by BRENDA team
-
higher PyNpase levels in tumor tissue than in normal tissue or tissue adjacent to the tumor, PyNpase levels independent of age, gender, history of recurrence, multiplicity, tumor size, tumor shape, pathological stage (Ta, T1-4), PyNpase levels differ between histological stages being highest in G3, and between papillary versus non-papillary growth pattern, higher PyPnase levels in high-risk group (G3 or Tis or T2) than in low-risk group (primary, single, G1 and Ta)
Manually annotated by BRENDA team
-
very high expression level
Manually annotated by BRENDA team
-
presurgery serum from 47 patients with ovarian cancer, and control serum from women with normal ovaries, treated surgically due to nononcological reasons. Significant higher enzyme activity in malignant serum specimen from ovarian cancer patients when compared to the control
Manually annotated by BRENDA team
Mus musculus C57Bl6/J
-
-
-
Manually annotated by BRENDA team
-
tumor specimen
Manually annotated by BRENDA team
-
ductal carcinoma in situ and invasive elements
Manually annotated by BRENDA team
-
diverse cancer types, overview
Manually annotated by BRENDA team
-
the enzyme is upregulated in many solid tumors
Manually annotated by BRENDA team
-
WiDR, HT29 and Lovo
Manually annotated by BRENDA team
-
patients with PD-ECGF/TP-positive tumors have a poorer prognosis than those with negative tumors
Manually annotated by BRENDA team
-
enzyme activity is higher in cancer tiddue than in adjacent normal tissue
Manually annotated by BRENDA team
-
thymidine phosphorylase shows a characteristic pattern of distribution dependent on the phase of the menstrual cycle: enzyme expression moves from stroma to epithelium as the cycle progresses34 and is inversely correlated with estradiol concentrations
Manually annotated by BRENDA team
-
patients with PD-ECGF/TP-positive tumors have a poorer prognosis than those with negative tumors
Manually annotated by BRENDA team
-
enzyme activity is higher in cancer tiddue than in adjacent normal tissue
Manually annotated by BRENDA team
-
poorly differentiated adenocarcinoma
Manually annotated by BRENDA team
Mus musculus C57Bl6/J
-
-
-
Manually annotated by BRENDA team
-
epidermoid
Manually annotated by BRENDA team
Mus musculus C57Bl6/J
-
-
-
Manually annotated by BRENDA team
-
cholangiocarcinoma-derived cell line, which has a naturally high level of endogenous thymidine phosphorylase
Manually annotated by BRENDA team
-
peripheral blood
Manually annotated by BRENDA team
-
no differences in thymidine phosphorylase activity between man and women or with increasing age
Manually annotated by BRENDA team
-
normal tissue
Manually annotated by BRENDA team
-
thymidine phosphorylase activity in normal liver tissue adjacent to hepatocellular carcinoma is related to tumor occurrence and may predict postoperative tumor recurrence. Patients who have a high thymidine phosphorylase level in normal liver tissue have significantly earlier recurrence compared with patients who have a low thymidine phosphorylase level. Patients who have a low thymidine phosphorylase level in adjacent liver tissue have a 0.387fold higher risk of postoperative recurrence compared with patients who have a high TP level
Manually annotated by BRENDA team
Mus musculus C57Bl6/J
-
-
-
Manually annotated by BRENDA team
-
the mean thymidine phosphorylase concentration in non-small cell lung cancer tissue is statistically higher than that of normal lung tissue
Manually annotated by BRENDA team
-
very high expression level
Manually annotated by BRENDA team
-
the cytoplasmic level of heterogeneous nuclear ribonucleoprotein K is significantly correlated with the elevated expression of thymidine phosphorylase, and high levels of both proteins are predictive of a poor prognosis in nasopharyngeal carcinoma
Manually annotated by BRENDA team
-
the mean thymidine phosphorylase concentration in non-small cell lung cancer tissue is statistically higher than that of normal lung tissue
Manually annotated by BRENDA team
-
similar distribution of thymidine phosphorylase and thymidine kinase, EC 2.7.1.21, immunohistochemical analysis, overview
Manually annotated by BRENDA team
-
the enzyme is strongly induced in the serum-deprived nasopharyngeal carcinoma cells, the serum deprivation-triggered upregulation of the enzyme is due to mRNA stabilization, not protein stabilization or transcriptional activation requiring the mRNA CU-rich element sequence and heterogeneous nuclear ribonucleoprotein K, overview
Manually annotated by BRENDA team
-
the enzyme is strongly induced in the serum-deprived nasopharyngeal carcinoma cells, the serum deprivation-triggered upregulation of the enzyme is due to mRNA stabilization, not protein stabilization or transcriptional activation requiring the mRNA CU-rich element sequence and heterogeneous nuclear ribonucleoprotein K, overview
Manually annotated by BRENDA team
-
the enzyme is strongly induced in the serum-deprived nasopharyngeal carcinoma cells, the serum deprivation-triggered upregulation of the enzyme is due to mRNA stabilization, not protein stabilization or transcriptional activation requiring the mRNA CU-rich element sequence and heterogeneous nuclear ribonucleoprotein K, overview
Manually annotated by BRENDA team
-
tissue from 47 patiens with ovarian cancer after surgery. Significant higher enzyme activity in malignant tissue from ovarian cancer patients when compared to the control
Manually annotated by BRENDA team
-
tissue from 47 patiens with ovarian cancer after surgery. Significant higher enzyme activity in malignant tissue from ovarian cancer patients when compared to the control
Manually annotated by BRENDA team
-
and adjacent nonmalignant pancreatic tissue
Manually annotated by BRENDA team
-
high expression level, two alternative enzyme forms, a 27 kDa splice variant and another form containing five additional amino acids on the N-terminus, the second form is processed at Thr6 instead of Ala11
Manually annotated by BRENDA team
Mus musculus C57Bl6/J
-
-
-
Manually annotated by BRENDA team
-
tumor tissue
Manually annotated by BRENDA team
-
surrounding cancer nests or along the invasive margin of cancer
Manually annotated by BRENDA team
-
fibroblast-like synoviocyte
Manually annotated by BRENDA team
-
rheumatoid athritis-associated
Manually annotated by BRENDA team
-
shows significantly greater activity in cancer tissues than in normal tissues
Manually annotated by BRENDA team
-
normal and tumor tissue
Manually annotated by BRENDA team
-
leiomyoma
Manually annotated by BRENDA team
-
from peripheral blood
Manually annotated by BRENDA team
additional information
-
no activity in normal brain
Manually annotated by BRENDA team
additional information
-
overview tumor cells
Manually annotated by BRENDA team
additional information
-
the enzyme is produced by macrophages and exists in neutrophils and cancer cells
Manually annotated by BRENDA team
additional information
-
not detected in most of non-tumoral glandular epithelial cells
Manually annotated by BRENDA team
additional information
-
enzyme expression analysis in cancer patients, overview
Manually annotated by BRENDA team
additional information
-
enzyme expression analysis in cell and tissues, overview
Manually annotated by BRENDA team
additional information
-
the enzyme is upregulated in a wide variety of solid tumors including breast and colorectal cancers, association of the enzyme with tumor grade is evident in bladder, cervical, and renal cell cancer, but not in the other investigated cancers, in most cases, the enzyme appeared to be associated with poor prognosis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
macrophages in rectal cancer tissue
Manually annotated by BRENDA team
-
neutrophil in gastric cancer tissue
Manually annotated by BRENDA team
additional information
-
the mechanism behind the secretion of thymidine phosphorylase is possibly a posttranslational process whereby serine residues of the enzyme are covalently linked to phosphate groups of nucleotides, leading to the formation of a nucleotidylated protein that can be secreted
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45000
-
SDS-PAGE
638469
52000
-
recombinant enzyme lacking 10 amino acid residues, SDS-PAGE
638466
55000
-
-
638463
55000
-
SDS-PAGE
638464, 638466
80000
-
gel filtration
638454
90000
-
gel filtration
638444
90000
-
-
638468
98000
-
-
638446
110000
-
gel filtration
638449
120000
-
gel filtration
638451
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
2 * 60000, SDS-PAGE
dimer
-
2 * 38000, SDS-PAGE
dimer
-
2 * 46000
dimer
-
2 * 58000, SDS-PAGE, enzyme is capable of being converted to a less active form larger in MW and possibly trimeric or tetrameric in structure
dimer
-
2 * 45000
dimer
-
2 * 47000, SDS-disc gel electrophoresis
dimer
-
two identical subunits, SDS-PAGE
dimer
-
three-dimensional structure, 2 identical subunits, each subunit is composed of a small alpha-helical domain and a large alpha/beta domain
dimer
-
x-ray crystallography
dimer
Escherichia coli K12
-
2 * 46000, three-dimensional structure, 2 identical subunits, each subunit is composed of a small alpha-helical domain and a large alpha/beta domain
-
dimer
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
2 * 47000, SDS-disc gel electrophoresis
-
homodimer
-
2 * 45000
homodimer
-
2 * 90000
homodimer
-
2 * 110000
homodimer
-
2 * 110000, about
additional information
-
dual substrate enzyme with two domains
additional information
-
each subunit contains a large mixed alpha-helical and beta-sheet domain, separated from a smaller alpha-helical domain by a large cleft. The active site consists of the thymine-binding site in the alpha-domain and the phosphate-binding site across the cleft in the a/b domain
additional information
-
three-dimensional enzyme structure by molecular dynamic simulation
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
two alternative enzyme forms, a 27 kDa splice variant and another form containing five additional amino acids on the N-terminus, the second form is processed at Thr6 instead of Ala11
additional information
-
the mechanism behind the secretion of thymidine phosphorylase is possibly a posttranslational process whereby serine residues of the enzyme are covalently linked to phosphate groups of nucleotides, leading to the formation of a nucleotidylated protein that can be secreted
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method
-
enzyme complexed with TPI
-
purified recombinant thymidine phosphorylase, free and in complex with 5-iodouracil, X-ray diffraction structure determination and analysis at 3.0 A and 2.5 A resolutions, respectively
-
structure of enzyme from crystals grown in the presence of thymidine
-
structure of HTP bound to the small molecule inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl)methyl]uracil hydrochloride, glutathione S-transferase fused to thymidine phosphorylase residues 12482 (based on Swissprot accession number P19971) via a thrombin-cleavable linker, crystallizationd at 15C using the hanging-drop vapor method
-
X-ray diffraction structure determination and analysis of the free enzyme at 3.5 A resolution, and of the in complex with the small and potent inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl)methyl] uracil at 2.1 A resolution
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6
-
maximal stability
638445
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
53
-
77% loss of activity after 10 min, phosphate or 2'-deoxyribose-1-phosphate stabilize
638452
55
-
99% loss of activity after 10 min, phosphate or 2'-deoxyribose-1-phosphate stabilize
638452
55
-
40 min, 10% loss of activity
638455
60
-
20 min, complete loss of activity
638455
65
-
30 min, complete inactivation
638449
additional information
-
phosphate or pentose 1-phosphate ester substrates stabilize against heat inactivation
638452
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
crystals are stable to X-rays at room temperature for at least 5 days
-
phosphate or pentose 1-phosphate ester substrates stabilize against heat inactivation
-
stability depends on protein concentration
-
stable to repeated freezing and thawing
-
2-mercaptoethanol and sucrose stabilize during preincubation procedure with ammonium sulfate
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 10 mM Tris-HCl, pH 7.3, stable for several months
-
4C, gradual loss of activity
-
-20C, phosphate buffer containing 2% mannitol, stable for over 1 year, human enzyme
-
4C, storage results in a decrease of the 120 kDA component, an increase of the high molecular weight component, and a loss of activity
-
5C, 90% loss of activity after 3-4 days
-
4C, 10 mM potassium phosphate, pH 7.5, 10 mM 2-mercaptoethanol, 20% sucrose, stable for 3 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
native enzyme
-
98% purity
-
ammonium sulfate fractionation
-
chromatography
-
homogeneity
-
Ni+-chelation-affinity chromatography
-
recombinant enzyme from Escherichia coli strain BL21(DE3) by calmodulin affinity chromatography, cleavage of the calmodulin binding protein tag by enterokinase, removal by chromatography on soybean trypsin inhibitor-sepharose
-
recombinant wild-type and mutan enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
-
separation of uridine phosphorylase and thymidine phosphorylase activities
-
homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Chinese hamster V-79 cells
-
expressed in CHO cells
-
expressed in Colo-320TP1 and C26A cells
-
expressed in Escherichia coli
-
expressed in Jurkat cells
-
expressed in V-79 hamster cells
-
expressed in V79 Chinese hamster cells
-
expression in KB cells
-
expression in rat vascular smooth muscle cell
-
expression of the calmodulin binding protein-tagged enzyme in Escherichia coli strain BL21(DE3) cells transformed with the pCal-n-EK/TP and pGroESL vectors
-
expression of wild-type and mutan enzymes in Escherichia coli strain BL21(DE3)
-
recombinant enzyme lacks 10 amino acids at amino-terminus
-
transfected into colon cancer cell line Colo320
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme expression is is inversely correlated with estradiol concentrations in the endometrium
-
capecitabine does not affect enzyme activity and expression
-
chorionic gonadotropin36 and a combination of progesterone and transforming growth factor b1 upregulate the enzyme expression. The enzyme is also upregulated in several diseases, detailed overview
-
the enzyme is strongly induced in the serum-deprived nasopharyngeal carcinoma cell lines TW-01, TW-02, and TW-04, the serum deprivation-triggered upregulation of the enzyme is due to mRNA stabilization, not protein stabilization or transcriptional activation requiring the mRNA CU-rich element sequence and heterogeneous nuclear ribonucleoprotein K, mechanism and kinetics, overview
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D203A
-
site-directed mutagenesis, the mutant enzyme shows 50fold reduced catalytic efficiency compared to the wild-type enzyme, the mutant also shows pronounced resistance to the inhibitory effect of 5'-O-tritylinosine, and it keeps full sensitivity to the competitive inhibitors 6-aminothymine and 6-amino-5-bromouracil
D203A
-
site-directed mutagenesis, the mutant shows 60% reduced phosphorolytic activity compared to the wild-type enzyme. The mutant is inhibited by 6-aminothymine 6-amino-5-bromouracil, like the wild-type enzyme, but not by 5'-O-tritylinosine, in contrast to the wild-type enzyme
H116F
-
site-directed mutagenesis, inactive mutant
H116K
-
site-directed mutagenesis, inactive mutant
I214A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
K115A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
K115E
-
inactive mutant
K115E
-
no enzyme activity after transfection in COS-7 cells
K115E
-
site-directed mutagenesis, inactive mutant
K115E
-
loss of enzymic activity. Expression of mutant in rat vascular smooth muscle cell does not have significant effect on cell proliferation
L148R
-
no enzyme activity after transfection in COS-7 cells
L148R
-
mutant devoid of enzymatic activity
R202E
-
site-directed mutagenesis, inactive mutant
R202S
-
no enzyme activity after transfection in COS-7 cells
R202S
-
site-directed mutagenesis, inactive mutant
R202S
-
loss of enzymic activity. Expression of mutant in rat vascular smooth muscle cell does not have significant effect on cell proliferation
S217G
-
site-directed mutagenesis, inactive mutant
Y199A
-
site-directed mutagenesis, inactive mutant
Y199F
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
L148R
-
loss of enzymic activity. Expression of mutant in rat vascular smooth muscle cell does not have significant effect on cell proliferation
additional information
-
downregulation of the enzyme by siRNA. Double knockout mutant cells, TP-/-UP-/-, lacking thymidine phosphorylase and uridine phosphorylase activities, show 100fold higher thymidine levels than the wild-type
additional information
-
gene silencing results in a significant increase in basal and oxidative stress-induced apoptosis, the effect is abrogated by supplementation with 2-deoxy-D-ribose-1-phosphate
Y199L
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
additional information
-
generation of double knockout mutant mice, TP-/-UP-/-, lacking thymidine phosphorylase and uridine phosphorylase activities, the mutant plasma thymidine levels are 5fold higher than in wild-type, but no alterations in mtDNA or pathological changes in the muscles occur in the knockout mice. Only in the brain, mitochondrial DNA depletion, respiratory chain defects and histological alterations, brain-specific phenotype, overview
additional information
-
generation of thymidine phosphorylase, TP, and uridine phosphorylase, UP, EC 2.4.2.3, double knockout mice, TP-/-UP-/- by insertion mutagenesis, which show severe TP deficiency, increased thymidine and deoxyuridine levels in tissues and elevated mitochondrial deoxythymidine triphosphate. As consequences of the nucleotide pool imbalances, brains of mutant mice developed partial depletion of mtDNA, deficiencies of respiratory chain complexes and encephalopathy, accounting for the pathogenesis of mitochondrial neurogastrointestinal encephalopathy, overview. Mitochondria respiratory chain deficiency in the brain of TP-/-UP-/- mice, overview
additional information
Mus musculus C57Bl6/J
-
generation of thymidine phosphorylase, TP, and uridine phosphorylase, UP, EC 2.4.2.3, double knockout mice, TP-/-UP-/- by insertion mutagenesis, which show severe TP deficiency, increased thymidine and deoxyuridine levels in tissues and elevated mitochondrial deoxythymidine triphosphate. As consequences of the nucleotide pool imbalances, brains of mutant mice developed partial depletion of mtDNA, deficiencies of respiratory chain complexes and encephalopathy, accounting for the pathogenesis of mitochondrial neurogastrointestinal encephalopathy, overview. Mitochondria respiratory chain deficiency in the brain of TP-/-UP-/- mice, overview
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
-
construction of Escherichia coli expression vector pDEOA and use of lactose instead of IPTG to induce expression. The use of lactose at concentrations above 0.5 mmol/l has an induction effect similar to that of IPTG but results in a longer initial induction time and better cell growth. The thymidine phosphorylase induced by lactose is very stable at 50C. Intact pDEOA cells induced by lactose can be used as a source of thymidine phosphorylase. Under standard reaction conditions, several deoxynucleosides are effectively produced from thymidine
synthesis
-
immobilization of enzyme on solid support with the aim to have a stable and recyclable biocatalyst for nucleoside synthesis. Immobilization by ionic adsorption on amine-functionalized agarose and Sepabeads results in more than 85% activity recovery. Cross-linking with aldehyde dextran, MW20 kDa, decreases the percentage of expressed activity after immobilization by about 25%, but results in up to 6fold and 3fold higher stability than the soluble enzyme and the non-cross-linked counterpart, respectively, at pH 10 and 37C. The preparation can be successfully used for the one-pot synthesis of 5-fluoro-2'-deoxyuridine starting from 2'-deoxyuridine or thymidine and 5-fluorouracil. In both cases, the reaction proceeds at the same rate leading to 62% conversion in 1 h
analysis
-
methods to measure thymidine and deoxyuridine concentrations and thymidine phosphorylase activity in biological samples. Thymidine phosphorylase activity can be measured by an endpoint determination of the thymine formed after 1 h incubation of the buffy coat homogenate in the presence of a large excess of its substrate thymidine, either spectrophotometrically or by HPLC-UV. The protocols allow the detection of thymidine phosphorylase dysfunction in patients with mitochondrial neurogastrointestinal encephalomyopathy, MNGIE
medicine
-
structural insight into the binding mode of the inhibitor to this important drug target forms the basis for designing novel inhibitors for use in anticancer therapy
medicine
-
thymidine phosphorylase activity might be useful in diagnostic characterization of ovarian cancer
medicine
-
tumor-associated macrophages that express thymidine phosphorylase may be a good target for chermotherapy of thymidine phosphorylase positive solid tumors
medicine
-
because pancreatic cancer is sensitive to 5-fluorouracil, thymidine phosphorylase-activated oral drug capecitabine in tumoral and endothelial cells and tumor infiltrating thymidine phosphorylase-positive macrophages could increase the concentration of 5-fluorouracil at tumor site, thus resulting in an enhanced antitumor activity
medicine
-
expression of PD-ECGF/TP may play an important role in the progression of solid tumors, and inhibitors of thymidine phosphorylase and analogs of the degradation products of thymidine may suppress the growth of tumors by promoting apoptosis
medicine
-
important target enzyme for cancer chemotherapy
medicine
-
mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive disorder characterized by ptosis and progressive external ophthalmoplegia, peripheral neuropathy, severe gastrointestinal dysmotility, cachexia and leukoencephalopathy, morphologically abnormal mitochondria and defects of respiratory chain enzymes. Patients harbor depletion, multiple deletions, and point mutations of mitochondrial DNA. This disorder is caused by loss-offunction mutations in the gene encoding thymidine phosphorylase. In patients with mitochondrial neurogastrointestinal encephalomyopathy, thymidine phosphorylase activity is very low or absent resulting in dramatically elevated levels of plasma thymidine and deoxyuridine. It is hypothesized that the increased levels of thymidine and deoxyuridine cause mitochondrial nucleotide pool imbalances that, in turn, generate mtDNA alterations
medicine
-
there is no tumour-selective depletion of thymidine and there does not appear to be any potential benefit of combining antibody-targeted thymidine phosphorylase with the thymidylate synthase inhibitor raltitrexed
medicine
-
thymidine phosphorylase activity in normal liver tissue adjacent to hepatocellular carcinoma is related to tumor occurrence and may predict postoperative tumor recurrence. Patients who have a high thymidine phosphorylase level in normal liver tissue have significantly earlier recurrence compared with patients who have a low thymidine phosphorylase level. Patients who have a low thymidine phosphorylase level in adjacent liver tissue have a 0.387fold higher risk of postoperative recurrence compared with patients who have a high TP level
medicine
-
thymidine phosphorylase expression is associated with response to capecitabine plus irinotecan in patients with metastatic colorectal cancer
medicine
-
thymidine phosphorylase expression seems to be an important prognostic indicator in gastric cancer patients only when the enzyme is located in tumor cells
medicine
-
a high level of thymidine phosphorylase gene expression is significantly associated with favorable diagnosis of patients treated with 5-fluorouracil-based chemotherapy
medicine
-
dThdPase plays an important role in tumor angiogenesis in ductal adenocarcinoma of the pancreas
medicine
-
expression of thymidine phosphorylase mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracilbased adjuvant chemotherapy
medicine
-
gliostatin and vascular endothelial growth factor have synergistic effects on angiogenesis in rheumatoid synovitis
medicine
-
immunhistochemical evaluation of thymidine phosphorylase expression is a promising predictor of therapeutic benefit from docetaxel-modulated capecitabine for metastatic breast cancer
medicine
-
in gastric cancer, thymidine phosphorylase expression of the cancer cells, not stromal cells may play an important role in tumor growth by microvessel formation
medicine
-
low tumour expression level of thymidine phosphorylase is linked with improved outcome for colorectal cancer patients treated with 5-fluorouracil, low thymidine phosphorylase protein expression is predictive of good response to 5-fluorouracil chemotherapy
medicine
-
the ThdPase expression in tumors may be a predictive marker for the effectiveness in response to chemotherapy with irinotecan and 5'-deoxy-5-fluoridine
medicine
-
the thymidine phosphorylase/dihydropyrimidine dehydrogenase ratio may be useful as prognostic factor in patients with pancreatic cancer
medicine
-
there is no significant association between the occurrence of palmar-plantar erythrodysesthesia after capecitabine treatment and higher tumor thymidine phosphorylase levels
medicine
-
thymidine phosphorylase delivers information about endometrial cancer progression
medicine
-
thymidine phosphorylase enzymatic activity may be associated with lymph node metastasis
medicine
-
thymidine phosphorylase expression at the invasive front of tumor may be an important prognostic factor for T3 rectal cancer
medicine
-
thymidine phosphorylase expression correlates well with tumor grade, metastasis and shorter patient survival in colorectal, pancreatic, renal, ovarian, cervical, bladder and non-small cell lung cancer, loss of function mutants of thymidine phosphorylase case the disease mitochondrial neurogastrointestinal encephalomyopathy
medicine
-
thymidine phosphorylase expression in breast cancer can represent a biomarker of sensitivity to capecitabine treatment
medicine
-
thymidine phosphorylase expression in cancer-infiltrating inflammatory cells can affect lymph node metastasis and patients' survival in gastric cancer
medicine
-
thymidine phosphorylase is a predictive biomarker in breast cancer
medicine
-
thymidine phosphorylase is a predictive factor of therapeutic efficacy of capecitabine chemotherapy for breast cancer
medicine
-
thymidine phosphorylase is a predictor of response to capecitabine-based chemotherapy in gastric cancer patients
medicine
-
thymidine phosphorylase is an independent prognostic and therapeutic marker for nasopharyngeal carcinoma
medicine
-
thymidine phosphorylase is associated with tumor angiogenesis
medicine
-
thymidine phosphorylase may be involved in up-regulating P-selectin expression in breast cancer cells, tumor cell thymidine phosphorylase correlates with tumor cell P-selectin but not with endothelial cell P-selectin in vascular endothelial cells
medicine
-
thymidine phosphorylase plays a role in oropharyngeal tumourigenesis and 5-fluorouracil activation in the adjuvant setting of oropharyngeal squamous cell carcinoma patients
medicine
-
thymidine phosphorylase serum levels reflect the prognosis of patients with colorectal cancer, particularly the risk of liver metastasis
medicine
-
thymidine phosphorylase is a promising target for the treatment of vascular obstructive diseases, effect on cancer cells, detailed overview
medicine
-
use of thymidine phosphorylase inhibitors might offer a promising strategy for cancer treatment
medicine
-
methods to measure thymidine and deoxyuridine concentrations and thymidine phosphorylase activity in biological samples. Thymidine phosphorylase activity can be measured by an endpoint determination of the thymine formed after 1 h incubation of the buffy coat homogenate in the presence of a large excess of its substrate thymidine, either spectrophotometrically or by HPLC-UV. The protocols allow the detection of thymidine phosphorylase dysfunction in patients with mitochondrial neurogastrointestinal encephalomyopathy, MNGIE