CEP-28122 (Mesylate salt)
CEP-28122 (Mesylate salt) 用途与合成方法
CEP-28122 mesylate salt (3-3000 nM; 48 hours) treatment leads to concentration-dependent growth inhibition of Karpas-299 and Sup-M2 cells in culture, associates with concentration-related caspase 3/7 activation. CEP-28122 mesylate salt (30-1000 nM; 2 hours) treatment leads to substantial suppression of phosphorylation of putative downstream effectors of ALK in Sup-M2 cells, indicating that the downstream signaling pathways are mediated by individual ALK fusion protein.
Cell Cytotoxicity Assay
| Cell Line: | Karpas-299, Sup-M2, Toledo and HuT-102 cells |
| Concentration: | 10 nM, 100 nM, 1000 nM, 10000 nM |
| Incubation Time: | 48 hours |
| Result: | Treatment led to concentration-dependent growth inhibition of Karpas-299 and Sup-M2 cells in culture. |
Western Blot Analysis
| Cell Line: | Sup-M2 cells |
| Concentration: | 30 nM, 100 nM, 300 nM, 1000 nM |
| Incubation Time: | 2 hours |
| Result: | Resulted in substantial suppression of phosphorylation of putative downstream effectors of ALK, including Stat-3, Akt, and ERK1/2 in Sup-M2 cells. |
CEP-28122 mesylate salt (3-30 mg/kg; oral gavage; twice a day; 12 days) produces dose-dependent antitumor activity in Sup-M2 subcutaneous tumor xenografts in SCID mice.In contrast, CEP-28122 has no antitumor activity in nu / nu mice bearing HCT116, suggesting that the antitumor activity of CEP-28122 in NPM-ALK–positive Sup-M2 tumor models is due to sustained NPM-ALK inhibition in tumors .
| Animal Model: | Female SCID mice bearing Sup-M2 subcutaneous tumor xenografts and nu / nu mice bearing HCT116 aged 6-8 week old |
| Dosage: | 3 mg/kg, 10 mg/kg and 30 mg/kg |
| Administration: | oral gavage; twice a day; 12 days |
| Result: | CEP-28122 produced dose-dependent antitumor activity in Sup-M2 subcutaneous tumor xenografts in SCID mice. In contrast, CEP-28122 had no antitumor activity in nu / nu mice bearing HCT116. |
