Zhang Dongna, Zhang Wenying, Liu He, Liu Pan, Li Chunxin, Liu Yangyang, Han Jicheng, Zhu Guangze
Department of Clinical Laboratory Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China.
Key Laboratory of Jilin Province for Traditional Chinese Medicine Prevention and Treatment of Infectious Diseases, College of integrative medicine, Changchun University of Chinese Medicine, Changchun, China.
Front Chem. 2024 Dec 10;12:1501844. doi: 10.3389/fchem.2024.1501844. eCollection 2024.
Recently, research into the oncogenic driver genes associated with non-small cell lung cancer (NSCLC) has advanced significantly, leading to the development and clinical application of an increasing number of approved therapeutic agents. Among these, small molecule inhibitors that target mesenchymal-epithelial transition (MET) have demonstrated successful application in clinical settings. Currently, three categories of small molecule MET inhibitors, characterized by distinct binding patterns to the MET kinase region, have been developed: types Ia/Ib, II, and III. This review thoroughly examines MET's structure and its crucial role in NSCLC initiation and progression, explores discovery strategies for MET inhibitors, and discusses advancements in understanding resistance mechanisms. These insights are anticipated to enhance the development of a new generation of MET inhibitors characterized by high efficiency, selectivity, and low toxicity, thereby offering additional therapeutic alternatives for patients diagnosed with NSCLC.
最近,与非小细胞肺癌(NSCLC)相关的致癌驱动基因的研究取得了显著进展,导致越来越多已获批治疗药物的开发和临床应用。其中,靶向间充质-上皮转化(MET)的小分子抑制剂已在临床环境中得到成功应用。目前,已开发出三类小分子MET抑制剂,其与MET激酶区域的结合模式各不相同:Ia/Ib型、II型和III型。本综述全面研究了MET的结构及其在NSCLC起始和进展中的关键作用,探索了MET抑制剂的发现策略,并讨论了在理解耐药机制方面的进展。预计这些见解将促进新一代高效、选择性高和低毒性的MET抑制剂的开发,从而为被诊断为NSCLC的患者提供更多治疗选择。