Inhibitors of anaplastic lymphoma kinase: a patent review

Importance of the field: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that belongs to the insulin receptor superfamily. Aberrant ALK activity has been implicated in the oncogenesis of human cancers as a fusion protein in anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, diffuse large B-cell lymphoma, systemic histiocytosis and NSCLC or through mutations in the full length protein in hereditary familial neuroblastoma. Thus, abrogation of ALK signaling through direct kinase inhibition has become an attractive therapeutic intervention point for a subset of genetically defined human cancers. Areas covered in this review: This manuscript provides a comprehensive review of the patent literature pertaining to ALK inhibitors and outlines their potential as anticancer therapeutic agents. What the reader will gain: The reader will gain an understanding of the major structural classes of ALK inhibitors and insights into the future of this class of drugs. Take home message: Multiple small-molecule ALK inhibitors have been reported with diverse chemical architecture, potency, kinase selectivity profiles and activity against potential resistance. The breadth of inhibitors combined with the recent discoveries of the involvement of ALK in lung, breast and colorectal cancers has kept the field advancing at a rapid pace.