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Literature summary extracted from

  • Bijnsdorp, I.V.; Comijn, E.M.; Padron, J.M.; Gmeiner, W.H.; Peters, G.J.
    Mechanisms of action of FdUMP[10]: metabolite activation and thymidylate synthase inhibition (2007), Oncol. Rep., 18, 287-291.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.1.1.45 medicine inhibitors of thymidylate synthase are used in the treatment of advanced colorectal carcinoma Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.1.1.45 5-fluoro-2'-deoxyuridine comparison with inhibitory effect of FdUMP[10] and 5-fluorouraci Mus musculus
2.1.1.45 5-Fluoro-2-deoxyuridine FUdR Mus musculus
2.1.1.45 5-fluoro-dUMP
-
 Mus musculus
2.1.1.45 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
2.1.1.45 5-fluorouracil comparison with inhibitory effect of FdUMP[10] and 5-fluoro-2'-deoxyuridine Mus musculus
2.1.1.45 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
2.1.1.45 GW1843U89 direct folate-based inhibitor Mus musculus
2.1.1.45 additional information combination of leucovorin and 5-fluorouracil 5FU-LV, IC50 0.00016 (FM3A/0 cell) Mus musculus
2.1.1.45 nolatrexed
-
 Mus musculus
2.1.1.45 pemetrexed direct folate-based inhibitor; inhibitory to cell growth even in cell lacking thymidylate synthase activity Mus musculus
2.1.1.45 raltitrexed direct folate-based inhibitor Mus musculus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.1.1.45 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

EC Number Organism UniProt Comment Textmining
2.1.1.45 Mus musculus
-
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.1.1.45 FM3A cell
-
 Mus musculus
-
2.1.1.45 FM3A cell FM3A/TK- cell, mouse mammary carcinoma derived cell, deficient in thymidine kinase Mus musculus
-
2.1.1.45 FM3A cell FM3A/TSc cell, mouse mammary carcinoma derived cell, deficient in thymidylate synthase Mus musculus
-
2.1.1.45 FM3A cell mouse mammary carcinoma derived cell Mus musculus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.1.1.45 5,10-methylenetetrahydrofolate + dUMP
-
 Mus musculus 7,8-dihydrofolate + dTMP
-
 ?
2.1.1.45 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

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.1.1.45 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]
2.1.1.45 0.0000028
-
 FM3A/0 cell Mus musculus 5-fluoro-dUMP
2.1.1.45 0.000005
-
 FM3A/0 cell Mus musculus 5-Fluoro-2-deoxyuridine
2.1.1.45 0.000016
-
 FM3A/0 cell Mus musculus raltitrexed
2.1.1.45 0.000022
-
 pH 7.4, 37°C Mus musculus FdUMP[10]
2.1.1.45 0.000036
-
 FM3A/0 cell Mus musculus pemetrexed
2.1.1.45 0.000164
-
 FM3A/0 cell Mus musculus GW1843U89
2.1.1.45 0.00031
-
 FM3A/0 cell Mus musculus 5-fluorouracil
2.1.1.45 0.00128
-
 FM3A/0 cell Mus musculus nolatrexed