Imexon

Imexon (BM 06002) is an iminopyrrolidone aziridine with anti-cancer activity. In Vitro: Imexon (BM 06002) induces oxidative stress in the ER, activates an ER stress response. Imexon (BM 06002) does not significantly alter the levels of eIF2B5, however there is a dose-dependent increase in the phosphorylation of eIF2alpha, as well as an increase in the levels of GTP exchange protein eIF2B2 in MiaPaCa-2, Panc-1, and BxPC3 cells^[1]. Imexon (BM 06002) induces single-stranded breaks in the human A375 melanoma cells but only significantly at the highest concentrations for each agent compared to controls. Imexon plus DTIC cytotoxicity is additive^[2]. Imexon (BM 06002) show inhibitory activities against MiaPaCa-2, Panc-1 and BxPC3, with IC₅₀s of 275.5 ± 54.2, 147.4 ± 4.7 and 355.7 ± 114.7 μM^[3]. In Vivo: Imexon (BM 06002) in combination with DTIC results in an increase in the peak plasma imexon level in non-tumor-bearing mice. The combination of both drugs increases plasma imexon AUC by 22% (p=0.026). Imexon (BM 06002) (100 mg/kg/day, i.v.) treatment decreases the body weight of SCID mice bearing human A375 melanoma tumors, but there is no significant difference in tumor growth^[2]. Imexon (BM 06002) (100 mg/kg) in combination with GEM shows synergistic inhibition of Panc-1 tumor growth in SCID mice.