基于ALK的双抑制剂治疗癌症的研究进展

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2025-03-27 DOI:10.1016/j.bioorg.2025.108417

Jin-Feng Chen , Shu-Jin Guo , Bin He , Wei Zheng , Wen-Jie Jiang , Zhuo Yuan , Yu Xiang , Cheng Peng , Wei Xiong , Jian-You Shi

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引用次数: 0

摘要

间变性淋巴瘤激酶（ALK）编码高度保守的酪氨酸激酶受体（RTK），对许多肿瘤的发生和进展非常重要，尤其是非小细胞肺癌（NSCLC）。目前，第三代ALK抑制剂用于治疗ALK突变型NSCLC，但在治疗过程中迅速出现耐药性，极大地限制了其临床疗效。与单靶点抑制剂相比，由于ALK和其他参与肿瘤进展的相关靶点的协同作用，ALK双靶点抑制剂具有减少耐药出现、提高治疗疗效和优化药代动力学特征的优点。因此，我们概述了ALK双抑制剂的发展，重点介绍了它们的设计方法和构效关系（SAR），并对该领域的新挑战和潜在的未来方向提出了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Advances of dual inhibitors based on ALK for the treatment of cancer

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Advances of dual inhibitors based on ALK for the treatment of cancer

Anaplastic lymphoma kinase (ALK), which encodes a highly conserved receptor tyrosine kinase (RTK), is important for the development and progression of many tumors, especially non-small cell lung cancer (NSCLC). Currently, third-generation ALK inhibitors are used to treat ALK-mutant NSCLC, but the rapid emergence of resistance during treatment greatly limits their efficacy in clinic. In comparison to single-target inhibitors, ALK dual inhibitors offer the benefits of reducing the emergence of drug resistance, improving treatment efficacy, and optimizing pharmacokinetic features due to the synergistic function of ALK and other associated targets involved in tumor progression. Therefore, we outline the development of ALK dual inhibitors, highlight their design approaches and structure-activity relationship (SAR), and offer insights into new challenges and potential future directions in this area.

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.