Recent advances in the development of dual ALK/ROS1 inhibitors for non-small cell lung cancer therapy,European Journal of Medicinal Chemistry

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Recent advances in the development of dual ALK/ROS1 inhibitors for non-small cell lung cancer therapy
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2023-05-18 , DOI: 10.1016/j.ejmech.2023.115477
Yingxue Li ₁ , Yanna Lv ₁ , Cheng Zhang ₁ , Binyu Fu ₁ , Yue Liu ₁ , Jinxing Hu ₁

Affiliation

As a member of the insulin-receptor superfamily, ALK plays an important role in regulating the growth, proliferation, and survival of cells. ROS1 is highly homologous with ALK, and can also regulate normal physiological activities of cells. The overexpression of both is closely related to the development and metastasis of tumors. Therefore, ALK and ROS1 may serve as important therapeutic targets in non-small cell lung cancer (NSCLC). Clinically, many ALK inhibitors have shown powerful therapeutic efficacy in ALK and ROS1-positive NSCLC patients. However, after some time, patients inevitably develop drug resistance, leading to treatment failure. There are no significant drug breakthroughs in solving the problem of drug-resistant mutations. In this review, we summarize the chemical structural features of several novel dual ALK/ROS1 inhibitors, their inhibitory effect on ALK and ROS1 kinases, and future treatment strategies for patients with ALK and ROS1 inhibitor-resistant mutations.

中文翻译：

ALK/ROS1双抑制剂治疗非小细胞肺癌的最新进展

作为胰岛素受体超家族的一员，ALK 在调节细胞的生长、增殖和存活中发挥着重要作用。 ROS1与ALK高度同源，也能调节细胞的正常生理活动。两者的过度表达与肿瘤的发生、转移密切相关。因此，ALK和ROS1可能作为非小细胞肺癌（NSCLC）的重要治疗靶点。临床上，许多ALK抑制剂对ALK和ROS1阳性NSCLC患者显示出强大的治疗功效。然而，一段时间后，患者不可避免地会产生耐药性，导致治疗失败。解决耐药突变问题尚无重大药物突破。在这篇综述中，我们总结了几种新型 ALK/ROS1 双重抑制剂的化学结构特征、它们对 ALK 和 ROS1 激酶的抑制作用，以及针对 ALK 和 ROS1 抑制剂耐药突变患者的未来治疗策略。

更新日期：2023-05-18

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