Axl激酶抑制剂的研究进展

发布时间：2018-03-10 12:41

本文选题：Axl激酶抑制剂　切入点：抗肿瘤活性　出处：《中国新药杂志》2016年11期 　论文类型：期刊论文

【摘要】：Axl激酶属于受体酪氨酸激酶TAM家族,与配体Gas 6结合可激活Axl的酪氨酸激酶活性,从而活化其下游的信号转导通路,参与细胞的生长、迁移、聚集和凋亡等进程。近期研究表明,Axl激酶在多种癌症中都存在超表达或激活,特别是在经过化疗和受体酪氨酸激酶抑制剂(TKI)治疗后产生抗药性的癌细胞中,Axl的超表达现象尤为严重,是产生耐药性的重要原因之一,因此,Axl激酶抑制剂是治疗癌症的一个新策略。本文旨在介绍Axl激酶在癌症细胞中的作用,并探讨近年来发现的Axl信号通路在产生耐药性肿瘤中的作用,以及Axl抑制剂与其他癌症药物联合应用时所起到的协同作用。最后,我们对目前所发现的不同结构类型Axl激酶抑制剂的结构特点和它们在体外的生物活性以及动物体内的药效进行了总结。
[Abstract]:Axl kinase belongs to TAM family of receptor tyrosine kinase, which can activate tyrosine kinase activity of Axl by binding to ligand Gas 6, thus activating its downstream signal transduction pathway and participating in cell growth and migration. Recent studies have shown that axl kinase is overexpressed or activated in many cancers. In particular, the overexpression of axl is especially serious in cancer cells that develop resistance after chemotherapy and receptor tyrosine kinase inhibitor TKI, which is one of the important reasons for drug resistance. Therefore, axl kinase inhibitor is a new strategy for the treatment of cancer. The purpose of this paper is to introduce the role of Axl kinase in cancer cells, and to explore the role of Axl signaling pathway in the production of drug-resistant tumors, which has been discovered in recent years. And the synergistic effect of Axl inhibitors in combination with other cancer drugs. Finally, We summarized the structural characteristics of different structural types of Axl kinase inhibitors and their biological activities in vitro as well as their pharmacological effects in vivo.
【作者单位】：广东东阳光药业有限公司新药所;美国加拓科学公司;
【基金】：国家“重大新药创制”科技重大专项资助项目(2015ZX09101013)
【分类号】：R96

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