Anaplastic lymphoma kinase inhibitors: an updated patent review (2014–2018)

Introduction: Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase, has been discovered in several cancers, including anaplastic large-cell lymphoma, non-small cell lung cancer, and inflammatory myofibroblastic tumors. The deregulation of ALK activities, such as translocation and point mutation, results in human carcinogenesis. The use of ALK inhibitors in clinical cancer treatment has been shown to be efficacious, and the issue of resistance to ALK inhibitors has been reported. Consequently, the development of a new generation of ALK inhibitors is necessary. Areas covered: This paper provides a comprehensive review of the patent literature from 2014 to 2018 including small molecule ALK inhibitors and their use as anticancer agents. The approved and developing ALK inhibitors are described. Expert commentary: The available three generations of ALK inhibitors have shown a good anticancer effect in ALK-positive non-small cell lung cancer. An urgent issue in this field is ALK resistance development. The development of new ALK inhibitors through structure modification of currently available ALK inhibitors is proceeding, such as the synthesis of macrocyclic compounds. This article arranges the ALK inhibitors that have published in the patent in recent years. It may help in the investigation of a new generation of ALK inhibitors, which can overcome the resistance issue and development of novel drug candidates in the future.