Background

ASP3026 is a selective inhibitor of ALK with IC50 value of 3.5 nM [1].

ASP3026 is a potent ALK inhibitor and has a different selectivity with the reported ALK inhibitor crizotinib. When tested with a panel of 86 tyrosine kinases, ASP3026 showed the highest selectivity for ALK, ROS and ACK kinases. In NCI-H2228 NSCLC cells expressing EML4-ALK, five-day treatment of ASP3026 resulted in a cell growth inhibition with IC50 value of 64.8 nM. ASP3026 also inhibited the viability of NPM-ALK+ ALCL cells with IC50 values of 0.4, 0.75, 1 and 2.5 M in SU-DHL-1, SUP-M2, SR-786 and Karpas 299 cells, respectively [2, 3].

In mouse model with NCI-H2228 subcutaneous xenograft, oral administration of ASP3026 caused significant reduction of phosphorylated ALK and tumor growth. 30 mg/kg/d ASP3026 for 2 weeks induced tumor regression by 78%. In mice injected with Karpas 299 cells, ASP3026 treatment caused remarkable lymphoma regression [2, 3].

References:
[1] Kuromitsu S, Mori M, Shimada I, et al. Anti-tumor activity of ASP3026, a novel and selective ALK inhibitor of anaplastic lymphoma kinase (ALK).Annual Meeting of the American Association for Cancer Research (AACR), Orlando, FL. 2011.
[2] Mori M, Ueno Y, Konagai S, et al. The Selective Anaplastic Lymphoma Receptor Tyrosine Kinase Inhibitor ASP3026 Induces Tumor Regression and Prolongs Survival in Non