OSI-7904L

OSI-7904L (GW1843; 1843U89; OSI-7904) is a thymidylate synthase (TS) inhibitor with a K_i of 90 pM. OSI-7904L blocks de novo synthesis of thymidine nucleotides, DNA synthesis and induces cell death. OSI-7904L inhibits the growth of human cells, induces tumor regression, and achieves durable antitumor effects in mouse xenograft models. OSI-7904L can be used in research related to colon adenocarcinoma^[1][2]. In Vitro:OSI-7904L potently inhibits the growth of all tested human cell lines with sub-1 nM IC₅₀, with thymidine alone reversing this effect; murine cell lines are 80-1300-fold less sensitive than human cell lines^[2]. In Vivo:OSI-7904L (7.5 mg/kg; i.v.; every other day; 14 days) achieves 97.5% TGI, 83% tumor regression in HCT-8 TK^-/^- tumor-bearing Nu/Nu mice^[1].
OSI-7904L (7.5-25 mg/kg; i.v.; three distinct schedules: daily × 5 for 2 weeks, on days 1,3,5 for 2 weeks, or on days 1 and 8) achieves 95-97% TGI, 86-88% tumor regression, and 1 durable cure per group in HCT-8 TK^-/- tumor-bearing Nu/Nu mice^[1].
OSI-7904L (5-25 mg/kg; i.v.; on days 1 and 8) produces a dose-dependent response in HCT-8 TK^-/- tumor-bearing Nu/Nu mice, with 80-99% TGI, 0-100% tumor regression, and 0-4 durable cures at day 60^[1].