摘要
非小细胞性肺癌是一个特别严重的癌症,可选择的药物依旧在研究当中。间变性淋巴瘤激酶(ALK)是一个属于胰岛素受体家族的络氨酸激酶受体。EML4-ALK融合基因作为一种新的分子集2007年在非小细胞性肺癌病人身上初步识别,这对于间变性淋巴瘤激酶有着高敏感度。自从2011年,美国食品药品监督管理局批准了第一个间变性淋巴瘤激酶抑制剂克唑替尼治疗非小细胞性肺癌以来,间变性淋巴瘤激酶一直被作为是治疗非小细胞性肺癌有前景的靶向药物。然而,克唑替尼并不是对于各种间变性淋巴瘤激酶点突变和控制神经系统转移都有效。最新研究,仅仅只有八种在临床调查和其他前期临床研究的二代和三代间变性淋巴瘤激酶抑制剂。这篇综述总结了间变性淋巴瘤激酶抑制剂在他们生物活性、选择性和结构-活性关系信息方面的最新研究进展。我们希望这篇综述能够帮助医学化学家发现跟新的间变性淋巴瘤激酶抑制剂克服现今在药物探索像潜在性、选择性和二次转移进程中存在的问题。
关键词: 间变性淋巴瘤激酶,非小细胞性肺癌,限制因素,点突变,生物活性,ASR。
Current Medicinal Chemistry
Title:Recent Development in the Discovery of Anaplastic Lymphoma Kinase (ALK) Inhibitors for Non-small Cell Lung Cancer
Volume: 24 Issue: 6
关键词: 间变性淋巴瘤激酶,非小细胞性肺癌,限制因素,点突变,生物活性,ASR。
摘要: Non-Small Cell Lung Cancer (NSCLC) is an especially aggressive cancer, the optimal drugs for which are still being developed. The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase belonging to the insulin receptor superfamily. EML4-ALK fusion gene initially identified in patients with NSCLC in 2007 is defined as a new molecular subset, which is highly sensitive to ALK inhibition. Since the first ALK inhibitor, crizotinib, was approved by the US Food and Drug Administration (FDA) for the treatment of NSCLC patients in 2011, ALK has been identified as a promising target for NSCLC therapy. However, crizotinib is not effective for various point mutations in ALK and central nervous system (CNS) metastasis. To date, there are only eight of second-and third-generation ALK inhibitors in clinical investigation and others are in preclinical research. This review summarizes recent advances of ALK inhibitors, with a focus on their biological activity, selectivity and structure-activity relationship (SAR) information. We hope this review could help medicinal chemists to discover newer ALK-inhibitors to overcome exist issues in the process of drug discovery, such as potency, selectivity and secondary mutations.
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Recent Development in the Discovery of Anaplastic Lymphoma Kinase (ALK) Inhibitors for Non-small Cell Lung Cancer, Current Medicinal Chemistry 2017; 24 (6) . https://dx.doi.org/10.2174/0929867323666161029223823
DOI https://dx.doi.org/10.2174/0929867323666161029223823 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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