AP26113

AP26113 is a potent and selective active inhibitor of anaplastic lymphoma kinase(ALK) with IC50 of 0.62 nM.
　　IC50 Value: 0.62 nM (ALK); 30.8 nM (Growth inhibition of EML4-ALK or NPM-ALK positive NSCLC and ALCL cell lines) [1]
　　Target: ALK
　　in vitro: AP-26113 exhibited approx 100-fold selectivity for ALK-positive lines compared with a approx 10-fold selectivity for PF-1066. At the highest doses tested, strong regressions were achieved with AP-26113, but not PF-1066 .AP-26113 inhibited the tumor growth at 25 mg/kg in ALCL and at 10 mg/kg in NSCLC models [1]. AP26113 inhibits cell growth with IC50 of 11 nM and 16 nM in Ba/F3 line (native EML4-ALK) and Ba/F3 line (EML4-ALK G1269S mutants). AP26113 inhibits ALK phosphorylationh with IC50 of 74 nM and 335 nM in Ba/F3 line (native EML4-ALK) and Ba/F3 line (EML4-ALK E1210K mutants). AP26113 (10 mg/kg-75 mg/kg) is efficacious in PF-02341066-resistant EML4-ALK mutant mouse xenograft models. AP26113 induces regression of tumors expressing native EML4-ALK and the G1269S and L1196M mutants at 25 mg/kg, 50 mg/kg and 50 mg/kg, respectively [2].
　　in vivo: In animal models, AP-26113 was well-tolerated at and above predicted clinically effective plasma levels [1]. AP26113 also exhibited similar potency against HCC827 cells expressing either EGFR-DEL or EGFR-DEL/T790M in a xenograft model, with daily oral doses of 25 mg/kg or greater leading to tumor regression in both models [3].
　　Clinical trial: A Phase I/II Study of the Oral ALK/EGFR Inhibitor AP-26113. Phase1/ Phase2


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