Department of Biotechnology, Konkuk University, Chungju 27478, Republic of Korea.
Research Institute for Biomedical & Health Science, Konkuk University, Chungju 27478, Republic of Korea.
Int J Mol Sci. 2023 Mar 18;24(6):5821. doi: 10.3390/ijms24065821.
The (echinoderm microtubule-associated protein-like 4)- (anaplastic lymphoma kinase) fusion gene in non-small-cell lung cancer (NSCLC) was first identified in 2007. As the EML4-ALK fusion protein promotes carcinogenesis in lung cells, much attention has been paid to it, leading to the development of therapies for patients with NSCLC. These therapies include ALK tyrosine kinase inhibitors and heat shock protein 90 inhibitors. However, detailed information on the entire structure and function of the EML4-ALK protein remains deficient, and there are many obstacles to overcome in the development of novel anticancer agents. In this review, we describe the respective partial structures of EML4 and ALK that are known to date. In addition to their structures, noteworthy structural features and launched inhibitors of the EML4-ALK protein are summarized. Furthermore, based on the structural features and inhibitor-binding modes, we discuss strategies for the development of novel inhibitors targeting the EML4-ALK protein.
在非小细胞肺癌（NSCLC）中首次发现的（棘皮动物微管相关蛋白样 4）-（间变性淋巴瘤激酶）融合基因于 2007 年被确定。由于 EML4-ALK 融合蛋白促进肺细胞的癌变，因此引起了人们的极大关注，从而为 NSCLC 患者开发了治疗方法。这些疗法包括 ALK 酪氨酸激酶抑制剂和热休克蛋白 90 抑制剂。然而，关于 EML4-ALK 蛋白的整个结构和功能的详细信息仍然不足，并且在开发新型抗癌药物方面存在许多障碍。在这篇综述中，我们描述了迄今为止已知的 EML4 和 ALK 的各自部分结构。除了它们的结构外，还总结了 EML4-ALK 蛋白的值得注意的结构特征和已推出的抑制剂。此外，基于结构特征和抑制剂结合模式，我们讨论了针对 EML4-ALK 蛋白开发新型抑制剂的策略。
