Anaplastic lymphoma kinase (ALK) is a promising therapeutic target for the treatment of cancers, including echinoderm microtubule-associated protein-like 4 (EML4)-ALK positive non-small cell lung cancer (NSCLC). We synthesized a series of 1,3,5-triazine derivatives as novel ALK inhibitors. ASP3026 potently and selectively inhibited ALK, and demonstrated dose-dependent antitumor activity in mice bearing NCI-H2228 tumor xenografts. ASP3026 also showed inhibitory activity against the L1196M gatekeeper mutant of ALK that confers resistance to crizotinib. Synthesis and structure-activity relationships of ASP3026 and its derivatives will be presented.

Discovery of ASP3026 as a potent and selective anaplastic lymphoma kinase (ALK) inhibitor for the treatment of non-small cell lung cancer

247th National Meeting (2014)

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