亚美克松

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. 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. Imexon (BM 06002) show inhibitory activities against MiaPaCa-2, Panc-1 and BxPC3, with IC ₅₀ s of 275.5 ± 54.2, 147.4 ± 4.7 and 355.7 ± 114.7 μM.

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. Imexon (BM 06002) (100 mg/kg) in combination with GEM shows synergistic inhibition of Panc-1 tumor growth in SCID mice.