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在非小细胞肺癌中鉴定一种靶向EML4-ALK融合蛋白的强效激酶抑制剂。

Identification of a potent kinase inhibitor targeting EML4-ALK fusion protein in non-small cell lung cancer.

作者信息

Luo Lian-Xiang, Li Ying, Niu Yu-Zhen, Wang Yu-Wei, Wang Qian-Qian, Fan Xing-Xing, Xu Jia-Hui, Liu Liang, Leung Elaine Lai-Han, Yao Xiao-Jun

机构信息

State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute For Applied Research in Medicine and Health , Macau University of Science and Technology , Macau SAR , China . Email:

State Key Laboratory of Applied Organic Chemistry and Department of Chemistry , Lanzhou University , Lanzhou 730000 , China.

出版信息

Medchemcomm. 2017 Aug 25;8(10):1914-1918. doi: 10.1039/c7md00305f. eCollection 2017 Oct 1.

DOI:10.1039/c7md00305f
PMID:30108712
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6071718/
Abstract

ALK-fusion proteins play a fundamental role in the development of about 5% of non-small cell lung cancers. Herein, we identified the compound 5067-0952 as a potent ALK inhibitor, which inhibited cell growth, induced apoptosis, and suppressed the phosphorylation of ALK, subsequently blocking its downstream signaling pathway.

摘要

ALK融合蛋白在约5%的非小细胞肺癌发生发展中起重要作用。在此,我们鉴定出化合物5067 - 0952为一种有效的ALK抑制剂,它可抑制细胞生长、诱导细胞凋亡,并抑制ALK的磷酸化,进而阻断其下游信号通路。

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本文引用的文献

1
Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial.塞瑞替尼与化疗用于既往接受过化疗和克唑替尼治疗的间变性淋巴瘤激酶(ALK)重排的非小细胞肺癌患者(ASCEND-5):一项随机、对照、开放标签、III 期临床试验。
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Cancer Statistics, 2017.《2017 年癌症统计》
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Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer.ALK 重排肺癌对第一代和第二代 ALK 抑制剂耐药的分子机制
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Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F.洛拉替尼的ALK耐药突变L1198F导致对克唑替尼重新致敏。
N Engl J Med. 2016 Jan 7;374(1):54-61. doi: 10.1056/NEJMoa1508887. Epub 2015 Dec 23.
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Crizotinib in ROS1-rearranged non-small-cell lung cancer.克唑替尼用于ROS1重排的非小细胞肺癌
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Molecular pathways: resistance to kinase inhibitors and implications for therapeutic strategies.分子途径:对激酶抑制剂的耐药性及其对治疗策略的影响
Clin Cancer Res. 2014 May 1;20(9):2249-56. doi: 10.1158/1078-0432.CCR-13-1610.
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Tyrosine kinase gene rearrangements in epithelial malignancies.上皮性恶性肿瘤中的酪氨酸激酶基因重排。
Nat Rev Cancer. 2013 Nov;13(11):772-87. doi: 10.1038/nrc3612. Epub 2013 Oct 17.
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Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology.ALK 受体酪氨酸激酶在人类癌症生物学中的作用机制研究。
Nat Rev Cancer. 2013 Oct;13(10):685-700. doi: 10.1038/nrc3580.