标题：Recent Development in the Discovery of Anaplastic Lymphoma Kinase (ALK) Inhibitors for Non-small Cell Lung Cancer
作者：Liu, Jingru; Ma, Shutao
作者机构：[Liu, Jingru; Ma, Shutao] Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rood, Jinan 250012, Peoples 更多
通讯作者地址：[Ma, ST]Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, 44 West Culture Rd, Jinan 250012, Peoples R China.
来源：CURRENT MEDICINAL CHEMISTRY
关键词：ALK; NSCLC; inhibitors; point mutations; biological activity; SAR
摘要：Non-Small Cell Lung Cancer (NSCLC) is an aggressive cancer, the optimal drugs for which are still being developed. The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase belonging to the insulin receptor superfamily. EML4-ALK fusion gene initially identified in patients with NSCLC in 2007 is defined as a new molecular subset, which is highly sensitive to ALK inhibition. Since the first ALK inhibitor, crizotinib, approved by the US Food and Drug Administration (FDA) for the treatment of NSCLC patients in 2011, ALK has been identified as a promising target for NSCLC therapy. However, crizotinib is not effective for various point mutations in ALK and central nervous system (CNS) metastasis. To date, there are only eight of second-and third-generation ALK inhibitors in clinical investigation and others are in preclinical research. This review summarizes recent advances of ALK inhibitors with a focus on their biological activity, selectivity and structure-activity relationship (SAR) information. We hope that this review could help medicinal chemists to discover newer ALK-inhibitors to overcome the existing issues in the process of drug discovery, such as potency, selectivity and secondary mutations.