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Literature summary for 2.1.1.45 extracted from
- Mechanisms of action of FdUMP[10]: metabolite activation and thymidylate synthase inhibition (2007), Oncol. Rep., 18, 287-291.
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | inhibitors of thymidylate synthase are used in the treatment of advanced colorectal carcinoma | Mus musculus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 5-fluoro-2'-deoxyuridine | comparison with inhibitory effect of FdUMP[10] and 5-fluorouraci | Mus musculus |  |
| 5-Fluoro-2-deoxyuridine | FUdR | Mus musculus | |
| 5-fluoro-dUMP | - |
Mus musculus | |
| 5-fluoro-dUMP[10] | a 10-mer of 5-fluoro-dUMP, a suicide inhibitor of thymidylate synthase, designed to bypass resistance to 5-fluorouracil, acts as a pro-drug of 5-fluoro-dUMP | Mus musculus | |
| 5-fluorouracil | comparison with inhibitory effect of FdUMP[10] and 5-fluoro-2'-deoxyuridine | Mus musculus | |
| FdUMP[10] | multimer of 5-fluoro-2'-deoxyuridine 5'-monophosphate, inhibits cell growth with greater potency than 5-fluorouracil and 5-fluoro-2'-deoxyuridine | Mus musculus | |
| GW1843U89 | direct folate-based inhibitor | Mus musculus | |
| additional information | combination of leucovorin and 5-fluorouracil 5FU-LV, IC50 0.00016 (FM3A/0 cell) | Mus musculus | |
| nolatrexed | - |
Mus musculus | |
| pemetrexed | direct folate-based inhibitor; inhibitory to cell growth even in cell lacking thymidylate synthase activity | Mus musculus | |
| raltitrexed | direct folate-based inhibitor | Mus musculus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5,10-methylenetetrahydrofolate + dUMP | Mus musculus | thymidylate synthase is an essential enzyme for de novo synthesis of thymidylate (dTMP), a precursor for DNA synthesis | 7,8-dihydrofolate + dTMP | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Mus musculus | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| FM3A cell | - |
Mus musculus | - |
| FM3A cell | FM3A/TK- cell, mouse mammary carcinoma derived cell, deficient in thymidine kinase | Mus musculus | - |
| FM3A cell | FM3A/TSc cell, mouse mammary carcinoma derived cell, deficient in thymidylate synthase | Mus musculus | - |
| FM3A cell | mouse mammary carcinoma derived cell | Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5,10-methylenetetrahydrofolate + dUMP | - |
Mus musculus | 7,8-dihydrofolate + dTMP | - |
? | |
| 5,10-methylenetetrahydrofolate + dUMP | thymidylate synthase is an essential enzyme for de novo synthesis of thymidylate (dTMP), a precursor for DNA synthesis | Mus musculus | 7,8-dihydrofolate + dTMP | - |
? | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.000000022 | - |
FdUMP[10] strongly inhibited cell growth in both FM3A cell lines, with a much lower resistance factor than FUdR and FdUMP | Mus musculus | FdUMP[10] | |
| 0.0000028 | - |
FM3A/0 cell | Mus musculus | 5-fluoro-dUMP | |
| 0.000005 | - |
FM3A/0 cell | Mus musculus | 5-Fluoro-2-deoxyuridine | |
| 0.000016 | - |
FM3A/0 cell | Mus musculus | raltitrexed | |
| 0.000022 | - |
pH 7.4, 37°C | Mus musculus | FdUMP[10] | |
| 0.000036 | - |
FM3A/0 cell | Mus musculus | pemetrexed | |
| 0.000164 | - |
FM3A/0 cell | Mus musculus | GW1843U89 | |
| 0.00031 | - |
FM3A/0 cell | Mus musculus | 5-fluorouracil | |
| 0.00128 | - |
FM3A/0 cell | Mus musculus | nolatrexed | |
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