ICI 198583

ICI 198583 is a thymidylate synthase (TS) inhibitor with a K_i value of 10 nM for both mouse and human TS. ICI 198583 serves as a substrate for folylpolyglutamate synthetase (FPGS) with a K_m of 40 μM. ICI 198583 exerts persistent, dose-dependent inhibition on thymidylate synthase flux in mice. ICI 198583 is applicable to relevant research on leukemia^[1]. In Vitro:ICI 198583 potently inhibits partially purified murine thymidylate synthase (TS) and human thymidylate synthase (TS), with a K_i of 10 nM^[1].
ICI 198583 serves as a substrate for partially purified mouse liver FPGS, with a K_m of 40 μM^[1].
ICI 198583 potently inhibits the proliferation of L1210 cells (IC₅₀ = 0.085 μM) and W1L2 cells (IC₅₀ = 0.056 μM) in vitro. It remains active against L1210:R7A cells overexpressing DHFR, while its activity against reduced folate transport-deficient L1210:1565 cells decreases by 96-fold^[1]. In Vivo:ICI 198583 (1-50 mg/kg; i.p.; once daily; for 5 consecutive days) exhibits potent therapeutic activity against L1210:ICR leukemia in male C57BL×DBA2 F1 hybrid mice^[1].
ICI 198583 (50-500 mg/kg; intravenous injection; single bolus) produces dose-dependent, sustained inhibition of thymidylate synthase in L1210:NCI leukemia cells of male C57BL×DBA2 F1 hybrid mice. After a single intravenous bolus of 500 mg/kg, the inhibition rate remains above 80% for 24 hours^[1].