| + |
ICI D1694 | down-regulates 
chemical inhibition
|
TYMS |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-206403 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
capecitabine | down-regulates activity
chemical inhibition
|
TYMS |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259354 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15866500 |
These findings suggest that the mechanism of antiproliferative toxicity of capecitabine is at least partly due to TS inhibitory activity of its active metabolite 5-fluoro-2'-deoxyuridine monophosphate (FdUMP). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
gemcitabine | down-regulates activity
chemical inhibition
|
TYMS |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259350 |
|
|
Homo sapiens |
A2780/100 Cell |
| pmid |
sentence |
| 25562513 |
2',2'-Difluoro-2'-deoxycytidine (dFdC, gemcitabine) is a cytidine analogue active against several solid tumor types, such as ovarian, pancreatic and non-small cell lung cancer. The compound has a complex mechanism of action. Because of the structural similarity of one metabolite of dFdC, dFdUMP, with the natural substrate for thymidylate synthase (TS) dUMP, we investigated whether dFdC and its deamination product 2',2'-difluoro-2'-deoxyuridine (dFdU) would inhibit TS. This study was performed using two solid tumor cell lines: the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000. The specific TS inhibitor Raltitrexed (RTX) was included as a positive control. Using the in situ TS activity assay measuring the intracellular conversion of [5-(3)H]-2'-deoxyuridine or [5-(3)H]-2'-deoxycytidine to dTMP and tritiated water, it was observed that dFdC and dFdU inhibited TS. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TYMS | up-regulates quantity 
chemical modification
|
dTMP(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268235 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21876188 |
In this pathway, 5,10-methyleneTHF, a one-carbon donor, is generated from serine by SHMT and used for the conversion of dUMP to dTMP in a reaction catalyzed by TYMS. The TYMS-catalyzed reaction generates dihydrofolate, which is converted to THF in an NADPH-dependent manner by DHFR. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TYMS | up-regulates quantity
chemical modification
|
dihydrofolate(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268232 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21876188 |
In this pathway, 5,10-methyleneTHF, a one-carbon donor, is generated from serine by SHMT and used for the conversion of dUMP to dTMP in a reaction catalyzed by TYMS. The TYMS-catalyzed reaction generates dihydrofolate, which is converted to THF in an NADPH-dependent manner by DHFR. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | One-carbon Metabolism |
| + |
TYMS | up-regulates
|
Purine biosynthesis |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253139 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21876188 |
In this pathway, 5,10-methyleneTHF, a one-carbon donor, is generated from serine by SHMT and used for the conversion of dUMP to dTMP in a reaction catalyzed by TYMS. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | One-carbon Metabolism |
| + |
pemetrexed disodium | down-regulates activity
chemical inhibition
|
TYMS |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259289 |
|
|
Homo sapiens |
Non-small Cell Lung Cancer Cell |
| pmid |
sentence |
| 14596699 |
Thymidylate synthase, the primary target of pemetrexed,9 is a fo-late-dependent enzyme that catalyzes the transformation of deoxyuri-dine monophosphate to deoxythymidine monophosphate. Inhibi-tion of TS results in decreased levels of thymidine, which is necessary for DNA synthesis. In addition to TS, pemetrexed inhibits DHFR, aminoimidazole carboxamide ribonucleotide formyltransferase (AICARFT), and glycinamide ribonucleotide formyltransferase (GARFT). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
pemetrexed | down-regulates
chemical inhibition
|
TYMS |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205933 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
MYC | up-regulates quantity by expression
transcriptional regulation
|
TYMS |
0.345 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-267374 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 18677108 |
Analysis of in vivo C-MYC interactions with TS, IMPDH2 and PRPS2 genes confirmed that they are direct C-MYC targets. C-MYC depletion did not significantly affect levels of E2F1 protein reported to regulate expression of many S-phase specific genes, but resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism. These included thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2). C-MYC depletion also resulted in reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TYMS | down-regulates quantity
chemical modification
|
dUMP(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268234 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21876188 |
In this pathway, 5,10-methyleneTHF, a one-carbon donor, is generated from serine by SHMT and used for the conversion of dUMP to dTMP in a reaction catalyzed by TYMS. The TYMS-catalyzed reaction generates dihydrofolate, which is converted to THF in an NADPH-dependent manner by DHFR. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CHD8 | up-regulates quantity by expression
transcriptional regulation
|
TYMS |
0.288 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268805 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 19255092 |
In order to identify CHD8 target genes, we performed a transcriptomic analysis of CHD8-depleted cells, finding out that CHD8 controls the expression of cyclin E2 (CCNE2) and thymidylate synthetase (TYMS), two genes expressed in the G1/S transition of the cell cycle. CHD8 was also able to co-activate the CCNE2 promoter in transient transfection experiments. Chromatin immunoprecipitation experiments demonstrated that CHD8 binds directly to the 5' region of both CCNE2 and TYMS genes. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
E2F1 | up-regulates quantity by expression 
transcriptional regulation
|
TYMS |
0.509 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253863 |
|
|
Homo sapiens |
HEP-3B Cell |
| pmid |
sentence |
| 14618416 |
To assess transactivating activity of E2F1/DP-1, we also analyzed expression of ten putative transcriptional targets of this complex in HCCs. Expression levels of TFDP1 and E2F1 correlated with those of seven transcriptional targets ( TYMS, DHFR, PCNA, RRM1, CCNE1, CDC2, and MYBL2) that play important roles in the G1/S transition, and down-regulation of TFDP1 inhibited growth of Hep3B cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
2',2'-difluoro-2'-deoxyuridine | down-regulates activity
chemical inhibition
|
TYMS |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259351 |
|
|
Homo sapiens |
A2780/100 Cell |
| pmid |
sentence |
| 25562513 |
2',2'-Difluoro-2'-deoxycytidine (dFdC, gemcitabine) is a cytidine analogue active against several solid tumor types, such as ovarian, pancreatic and non-small cell lung cancer. The compound has a complex mechanism of action. Because of the structural similarity of one metabolite of dFdC, dFdUMP, with the natural substrate for thymidylate synthase (TS) dUMP, we investigated whether dFdC and its deamination product 2',2'-difluoro-2'-deoxyuridine (dFdU) would inhibit TS. This study was performed using two solid tumor cell lines: the human ovarian carcinoma cell line A2780 and its dFdC-resistant variant AG6000. The specific TS inhibitor Raltitrexed (RTX) was included as a positive control. Using the in situ TS activity assay measuring the intracellular conversion of [5-(3)H]-2'-deoxyuridine or [5-(3)H]-2'-deoxycytidine to dTMP and tritiated water, it was observed that dFdC and dFdU inhibited TS. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
YBX1 | down-regulates quantity by repression 
transcriptional regulation
|
TYMS |
0.25 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-255613 |
|
|
Homo sapiens |
Ovary Cancer Cell |
| pmid |
sentence |
| 17072343 |
YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TFDP1 | up-regulates quantity by expression
transcriptional regulation
|
TYMS |
0.411 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253861 |
|
|
Homo sapiens |
HEP-3B Cell |
| pmid |
sentence |
| 14618416 |
To assess transactivating activity of E2F1/DP-1, we also analyzed expression of ten putative transcriptional targets of this complex in HCCs. Expression levels of TFDP1 and E2F1 correlated with those of seven transcriptional targets ( TYMS, DHFR, PCNA, RRM1, CCNE1, CDC2, and MYBL2) that play important roles in the G1/S transition, and down-regulation of TFDP1 inhibited growth of Hep3B cells. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
pralatrexate | down-regulates activity
chemical inhibition
|
TYMS |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259352 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 23409799 |
Pralatrexate is a small molecule with a chemical formula C23H23N7O5 and a molecular weight of 477.48 g/mol (Box 1). It competitively inhibits dihydrofolate reductase (DHFR) and thymidylate synthase. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TYMS | down-regulates quantity
chemical modification
|
(6R)-5,10-methylenetetrahydrofolate(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268231 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21876188 |
In this pathway, 5,10-methyleneTHF, a one-carbon donor, is generated from serine by SHMT and used for the conversion of dUMP to dTMP in a reaction catalyzed by TYMS. The TYMS-catalyzed reaction generates dihydrofolate, which is converted to THF in an NADPH-dependent manner by DHFR. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | One-carbon Metabolism |
3.0
TYMS
- 
- 