Literature summary for 2.1.1.45 extracted from

Giovannetti, E.; Backus, H.H.; Wouters, D.; Ferreira, C.G.; van Houten, V.M.; Brakenhoff, R.H.; Poupon, M.F.; Azzarello, A.; Pinedo, H.M.; Peters, G.J.
Changes in the status of p53 affect drug sensitivity to thymidylate synthase (TS) inhibitors by altering TS levels (2007), Br. J. Cancer, 96, 769-775.

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Application

Application	Comment	Organism
medicine	Lovo 175X2 cells transfected with mutant tumor suppressor gene p53 are more resistant to 5-fluorouracil, nolatrexed, raltitrexed and pemetrexed in comparison with the wild-type p53 parental cells Lovo 92. Resistance is associated with an increase in thymidylate synthase protein expression and catalytic activity. Lovo li cells, characterized by functionally inactive p53, are 3-13fold more sensitive to nolatrexed, raltitrexed and pemetrexed, and have a lower thymidylate synthase mRNA, protein expression and catalytic activity than Lovo 92. Mutant p53 WiDr cells transfected with wt p53 are not significantly different from mutant p53 WiDr cells with respect to sensitivity to thymidylate synthase inhibitors or thymidylate synthase levels	Homo sapiens
medicine	pharmacological treatment of colorectal cancer	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
5-fluorouracil	but a major mechanism of resistance to 5-fluorouracil is overexpression of thymidylate synthase	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
5,10-methylenetetrahydrofolate + dUMP	Homo sapiens	-	7,8-dihydrofolate + dTMP	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
LoVo cell	-	Homo sapiens	-
Lovo-175X2 cell	-	Homo sapiens	-
Lovo-92 cell	human colon carcinoma cell line	Homo sapiens	-
WiDr cell	-	Homo sapiens	-
WiDr cell	human colon carcinoma cell line	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
5,10-methylenetetrahydrofolate + dUMP	-	Homo sapiens	7,8-dihydrofolate + dTMP	-	?

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Release 2023.1 (January 2023)