| References: |
CEP-28122 is a potent inhibitor of recombinant ALK activity and cellular ALK tyrosine phosphorylation. It induced concentration-dependent growth inhibition/cytotoxicity of ALK-positive anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer (NSCLC), and neuroblastoma cells, and displayed dose-dependent inhibition of ALK tyrosine phosphorylation in tumor xenografts in mice, with substantial target inhibition (>90%) for more than 12 hours following single oral dosing at 30 mg/kg. Dose-dependent antitumor activity was observed in ALK-positive ALCL, NSCLC, and neuroblastoma tumor xenografts in mice administered CEP-28122 orally, with complete/near complete tumor regressions observed following treatment at doses of 30 mg/kg twice daily or higher. Treatment of mice bearing Sup-M2 tumor xenografts for 4 weeks and primary human ALCL tumor grafts for 2 weeks at 55 or 100 mg/kg twice daily led to sustained tumor regression in all mice, with no tumor reemergence for more than 60 days postcessation of treatment. Conversely, CEP-28122 displayed marginal antitumor activity against ALK-negative human tumor xenografts under the same dosing regimens. Administration of CEP-28122 was well tolerated in mice and rats. In summary, CEP-28122 is a highly potent and selective orally active ALK inhibitor with a favorable pharmaceutical and pharmacokinetic profile and robust and selective pharmacologic efficacy against ALK-positive human cancer cells and tumor xenograft models in mice. For the detailed information of CEP-28122, the solubility of CEP-28122 in water, the solubility of CEP-28122 in DMSO, the solubility of CEP-28122 in PBS buffer, the animal experiment (test) of CEP-28122, the cell expriment (test) of CEP-28122, the in vivo, in vitro and clinical trial test of CEP-28122, the EC50, IC50,and affinity,of CEP-28122, For the detailed information of CEP-28122, the solubility of CEP-28122 in water, the solubility of CEP-28122 in DMSO, the solubility of CEP-28122 in PBS buffer, the animal experiment (test) of CEP-28122, the cell expriment (test) of CEP-28122, the in vivo, in vitro and clinical trial test of CEP-28122, the EC50, IC50,and affinity,of CEP-28122, Please contact DC Chemicals. |
