CEP-28122 (mesylate salt)

CEP-28122 mesylate salt, a diaminopyrimidine derivative, is a potent, selective, and orally active ALK inhibitor with an IC₅₀ value of 1.9 nM. CEP-28122 mesylate salt has antitumor activity in experimental models of ALK-positive human cancers. CEP-28122 mesylate salt has good pharmacodynamic and pharmacokinetic activity. CEP-28122 mesylate salt can be used for the study of ALK-positive anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), and neuroblastoma cells^[1]. In Vitro:CEP-28122 (3-3000 nM; 48 hours) mesylate salt treatment leads to concentration-dependent growth inhibition of Karpas-299 and Sup-M2 cells in culture, associates with concentration-related caspase 3/7 activation^[1].
CEP-28122 (30-1000 nM; 2 hours) mesylate salt 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^[1]. In Vivo:CEP-28122 (3-30 mg/kg; oral gavage; twice a day; 12 days) mesylate salt 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 ^[1].