Idetrexed

Idetrexed (ONX 0801) is a thymidylate synthase (TS) inhibitor with a K_i of 1.2 nM. Idetrexed can be specifically transported into α-folate receptor (α-FR)-overexpressing tumors, such as ovarian cancer^[1][2]. In Vitro:Idetrexed (BGC 945) is designed to further reduce toxicity by more effectively targeting cancer cells that overexpress the α-FR^[1].
Idetrexed (BGC 945) exhibits IC₅₀ values of of 6.6 μM, 1.1 nM, 3.3 nM, 90 nM and 0.32 μM in A431, A431-FBP, KB, IGROV-1 and JEG-3 cells^[2].
In Vivo:Idetrexed (BGC 945) (100 mg/kg, ip/iv injection) in the tumor had a longer half-life (28 hours) compared with other tissues^[2].
Idetrexed (BGC 945) (100 mg/kg daily for 16 days) does not lead to body weight loss, macroscopic signs of toxicity to the major organs, or a change in renal function^[2].
Idetrexed (BGC 945) at 100 mg/kg induces a 5-20-fold increase in tumor dUrd at 4-72 h without increases in the plasma, consistent with tumor targeting^[2].