| + |
methotrexate | down-regulates activity 
chemical inhibition
|
DHFR |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258481 |
|
|
Homo sapiens |
Cancer Stem Cell |
| pmid |
sentence |
| 23581023 |
Methotrexate, a structural analogue of folic acid, is one of the most frequently used chemotherapeutics, especially in haematological malignancies, various solid tumours and also inflammatory disorders. Methotrexate interferes with folate metabolism, mainly by inhibition of dihydrofolate reductase, resulting in the suppression of purine and pyrimidine precursor synthesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
pemetrexed disodium | down-regulates activity
chemical inhibition
|
DHFR |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259290 |
|
|
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 |
| + |
DHFR | up-regulates quantity 
chemical modification
|
(6S)-5,6,7,8-tetrahydrofolate(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268258 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21876184 |
Human dihydrofolate reductase (DHFR) was previously thought to be the only enzyme capable of the reduction of dihydrofolate to tetrahydrofolate; an essential reaction necessary to ensure a continuous supply of biologically active folate. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | One-carbon Metabolism |
| + |
trimetrexate | down-regulates activity
chemical inhibition
|
DHFR |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258482 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 7981057 |
We examined the cytotoxicity and biochemical effects of the lipophilic antifol trimetrexate (TMQ) in two human colon carcinoma cell lines, SNU-C4 and NCI-H630, with different inherent sensitivity to TMQ. Dihydrofolate reductase (DHFR) and thymidylate synthase were quantitatively and qualitatively similar in both lines. During drug exposure, DHFR catalytic activity was inhibited by > or = 85% in both cell lines |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
pralatrexate | down-regulates activity
chemical inhibition
|
DHFR |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257815 |
|
|
Homo sapiens |
NCI-H460 Cell |
| pmid |
sentence |
| 19221750 |
This study reports a head-to-head comparison of in vitro and in vivo activities of three antifolates: pralatrexate, methotrexate, and pemetrexed. A clear difference was demonstrated among the antifolates in regulation of enzymatic activity. Pralatrexate demonstrated a unique activity profile relative to methotrexate and pemetrexed |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259353 |
|
|
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: |
2 |
Organism: |
Homo Sapiens |
| + |
pemetrexed | down-regulates
chemical inhibition
|
DHFR |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-205819 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TFDP1 | up-regulates quantity by expression 
transcriptional regulation
|
DHFR |
0.415 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253860 |
|
|
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 |
| + |
DHFR | down-regulates quantity
chemical modification
|
dihydrofolate(2-) |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268257 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 21876184 |
Human dihydrofolate reductase (DHFR) was previously thought to be the only enzyme capable of the reduction of dihydrofolate to tetrahydrofolate; an essential reaction necessary to ensure a continuous supply of biologically active folate. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | One-carbon Metabolism |
| + |
E2F1 | up-regulates quantity by expression
transcriptional regulation
|
DHFR |
0.517 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253853 |
|
|
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 |
3.0
DHFR
- 
- 