Trifluorothymidine的生物活性

Trifluorothymidine (TFT) and is an inhibitor of thymidine phosphorylase. TFT also inhibits thymidylate synthase (TS), a rate-limiting enzyme of DNA biosynthesis, and is incorporated into DNA.
IC50 Value: 1 uM ( Hela cell) [1]
Target: thymidylate synthase; Nucleoside antimetabolite/analog
Trifluorothymidine (TFT) is well known to be converted to TFT-monophosphate by thymidine kinase and to inhibit thymidylate synthase
in vitro: When HeLa cells were treated with TFT at a concentration of 1 uM (IC50 value), the concentration of TFT in the DNA was calculated as 62.2±0.9 pmol/1x106 cells for 4 h [1]. Unlike FdUrd and 5FU, TFT resulted in an earlier phosphorylation of ATR and chk1 proteins after only 24 h of exposure, while phosphorylated ATM, BRCA2 and chk2 proteins were detected after more than 48 h of exposure to TFT [2]. SN38 and TFT induced most DNA damage in H630 and Colo320 cells, which was increased in combination. TFT pre-incubation further enhanced SN38-induced DNA strand breaks in H630 and Colo320 (>20%), which was most pronounced in H630 cells (p<0.01) [3].
in vivo: After oral administration of TFT in rats, more than 75% of the TFT was absorbed [4].