Raltitrexed是一种抗代谢药物，通过抑制胸苷酸合成酶起作用，可用于化疗。

Raltitrexed（IC50 of 9 nM）, a thymidylate synthase inhibitor, is used for the inhibition of L1210 cell growth.

Raltitrexed induces double-stranded DNA breaks in a concentration-dependent manner. In Lovo cells and LS174T cell lines containing wild-type p53, Raltitrexed increases the levels of the Bax protein up to 5-fold. In human colon cancer cells, Raltitrexed is actively absorbed into cells and is then rapidly and extensively metabolized into a series of polyglutamates, which results in the effective inhibition of thymidylate synthase. Raltitrexed is delivered to the brain very quickly and can be detected in all brain tissues within 5 minutes. In human colon cancer cells, the combination of Raltitrexed and SN-38 results in a synergistic cytotoxic effect within a range of concentrations. Raltitrexed is a specific folate-based inhibitor of thymidylate synthase. The effect on the activity of advanced rectal cancer is similar to fluorouracil (5-fluorouracil) plus leucovorin. Raltitrexed produces activity by rapid cell entry and glutamination. The glutaminated derivatives are more than 100 times more active than the parent compound. In the HCT-8 cell line, Raltitrexed results in an increase in intracellular phosphoribosyl pyrophosphate (PRPD) indicating that the cytotoxic effect of Raltitrexed in combination with 5-FU is due to increased nucleotide formation of 5-FU. Combinations of Raltitrexed and folinic acid (5FU-FA) show a combination of mode-dependent, synergistic inhibition of proliferation, which is determined by measuring the combination series. Raltitrexed combined with Vorinostat produced significant synergistic effects of cell cycle perturbation and S-phase arrest.

Raltitrexed can be transported directly into the brain through the olfactory pathway in rats.

112887-68-0

C21H22N4O6S

458.49

ZD1694;雷替曲塞;D1694;ICI-D1694;Tomudex

H2O:<1 mgml
DMSO:84 mg/mL (183.2 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years